Clinical Trials Register

Summary
EudraCT Number:	2011-001459-35
Sponsor's Protocol Code Number:	MC/PR/1400/007/11
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-12-11
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2011-001459-35

A.3

Full title of the trial

MULTICENTRE, RANDOMISED, DOUBLE-BLIND, PARALLEL GROUP, PLACEBO-CONTROLLED STUDY ON THE THERAPEUTIC EFFICACY AND SAFETY OF BECLOMETHASONE DIPROPIONATE SUSPENSION FOR INHALATION 800 micrograms TWICE DAILY VS PLACEBO ADDED TO ANTIBIOTIC THERAPY IN PATIENTS WITH ACUTE RHINOSINUSITIS

Studio multicentrico, randomizzato, in doppio cieco, a gruppi paralleli, controllato verso placebo sull'efficacia terapeutica e sulla sicurezza della sospensione per inalazione di Beclometasone Dipropionato 800 microgrammi due volte al giorno verso placebo in aggiunta a terapia antibiotica in pazienti affetti da rinosinusite acuta

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

CLEAR

A.4.1

Sponsor's protocol code number

MC/PR/1400/007/11

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	CHIESI
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
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
B.5.2	Functional name of contact point	Eleonora Ingrassia
B.5.3	Address:
B.5.3.1	Street Address	via Palermo 26/1
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	0524 279526
B.5.5	Fax number	0521 279792
B.5.6	E-mail	e.ingrassia@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	CLENIL*AER 20FL 1D 0,8MG/2ML
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.3.4	Pharmaceutical form	Nebuliser 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	BECLOMETASONE DIPROPIONATE
D.3.9.1	CAS number	5534-09-8
D.3.9.2	Current sponsor code	CHF718
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	800
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Nebuliser 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

Acute rhinosinusitis

Rinosinusite acuta

E.1.1.1

Medical condition in easily understood language

Acute rhinosinusitis

Rinosinusite acuta

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	LLT
E.1.2	Classification code	10052106
E.1.2	Term	Rhinosinusitis
E.1.2	System Organ Class	100000004862

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 demonstrate that BDP suspension for inhalation twice a day for 14 days added to antibiotic therapy improves clinical success rate and accelerates recovery in patients with acute rhinosinusitis.

Dimostrare che la sospensione per inalazione di Beclometasone Dipropionato (BDP) somministrata due volte al giorno per 14 giorni in aggiunta a terapia antibiotica migliora il tasso di successo clinico e accelera la guarigione in pazienti affetti da rinosinusite acuta.

E.2.2

Secondary objectives of the trial

• To assess the time from baseline to a status of clinical success (cured or much improved); • To assess the rhinosinusitis symptoms during the treatment phase; • To assess the changes of overall sinus symptoms and tha changes of each symptoms; • To assess the level of work performance based on patient perception (recorded on a VAS scale of the diary card) and on missed working time; • To assess the number or recurrences assess the absence of relapses; • To assess the changes of nasal mucociliary transport time; • To assess the nasal air flow resistance with rhinomanometry; • To assess the safety profile of the investigational study drug.

-Valutare il tempo intercorrente tra il basale e lo stato di successo clinico (guarito o molto migliorato); -Valutare i sintomi di rinosinusite durante la fase di trattamento; -Valutare le variazioni complessive dei sintomi sinusali e le variazioni di ogni sintomo; -Valutare il livello di prestazione lavorativa basata sulla percezione del paziente (registrata mediante scala VAS sul diario) e il tempo di assenza dal lavoro; -Valutare l’assenza di recidive; -Valutare le variazioni nel tempo di trasporto muco ciliare nasale; -Valutare la resistenza nasale al flusso d’aria mediante rinomanometria; -Valutare il profilo di sicurezza del farmaco in studio.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects written informed consent obtained prior to any study-related procedures 2. Male and female out-patients aged between 18 and 65 years (inclusive). 3. History of previously diagnosed recurrent or chronic sinusitis that necessitated antibiotic therapy as judged by the investigator. 4. Clinical diagnosis of acute rhinosinusitis defined, according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (20), as the sudden onset of two or more relevant symptoms for <12 weels, one of which is: nasal blockage/obstruction/congestion OR nasal discharge (anterior/posterior nasal drip): AND the second one is: facial pain/pressure or/and reduction/loss of sense of smell. 5. A cooperative attitude and ability to be trained to use correctly the nebuliser with intranasal nose piece.

1. Consenso informato scritto ottenuto dal paziente prima di ogni procedura dello studio. 2. Pazienti ambulatoriali di sesso maschile o femminile di età compresa tra 18 e 65 anni (compresi). 3. Storia di sinusite ricorrente o cronica, precedentemente diagnosticata che abbia necessitato di terapia antibiotica a giudizio dello sperimentatore. 4. Diagnosi clinica di rinosinusite acuta definita, in accordo all’European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (20), come improvvisa comparsa di due o più sintomi rilevanti per meno di 12 settimane, uno dei quali è blocco/ostruzione/congestione nasale oppure secrezione nasale (gocciolamento nasale anteriore/posteriore): e il secondo è: dolore/pressione al volto e/o riduzione/perdita del senso dell’olfatto. 5. Atteggiamento collaborativo che gli permetta di apprendere l’uso corretto del nebulizzatore con il dispositivo intranasale.

E.4

Principal exclusion criteria

1. Previous sinus surgery; 2. Sinus lavage within the past 7 days; 3. Nasal polyposis or important nasal septum deviation; 4. Antibiotic use (by any route) in the past 30 days; 5. Recurrent moderate epistaxis; 6. Chronic bacterial sinusitis with evidence of failure of antimicrobial therapy; 7. Intranasal or systemic use of corticosteroids within the past 30 days; 8. Chronic use of corticosteroids or immunosuppressive agents; 9. Immunocompromised states; 10. Diagnosis of bronchial asthma or chronic obstructive pulmonary disease (COPD); 11. History of clinically significant cardiac (i.e. congestive heart failure or severe hypertension), renal (i.e. kidney failure), psychiatric (i.e. depression or mood disorders), hepatic (i.e. cholestatic jaundice or hepatic dysfunction), endocrine (i.e. hyperthyroidism or adrenal suppression) or pulmonary disease, or laboratory testing abnormalities, whose sequelae and/or treatments can interfere with the results or treatments of the present study; 12. History of psychiatric diseases likely to require treatment with antidepressant drugs during the study period or treatment with antidepressant drugs in the past 2 weeks; 13. Diagnosis of glaucoma or prostatic hypertrophy; 14. History of alcohol or drug abuse; 15. Allergy, sensitivity or intolerance to study drugs and/or study drugs formulations ingredients (e.g. corticosteroids ); 16. Pregnant or lactating women or all women physiologically capable of becoming pregnant 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: surgical sterilization (e.g. bilateral tubal ligation, hysterectomy) hormonal contraception (implantable, patch, oral) double-barrier methods (any double combination of: IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). A pregnancy test (urine) will be performed at screening in women of childbearing potential; 17. Patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; 18. Participation in another trial in the past 12 weeks or who patients have been previously enrolled in this study.

1. Precedente chirurgia nasale; 2. Lavaggi sinusali nei 7 giorni precedenti; 3. Poliposi nasali o deviazioni importanti del setto nasale; 4. Uso di antibiotici (attraverso qualsiasi via di somministrazione) nei precedenti 30 giorni; 5. Epistassi moderata ricorrente; 6. Sinusite batterica cronica con evidenza di fallimento della terapia antimicrobica; 7. Uso di corticosteroidi intranasali o sistemici nei 30 giorni precedenti; 8. Uso cronico di corticosteroidi o agenti immunosoppressori; 9. Soggetti immunocompromessi; 10. Diagnosi di asma bronchiale e malattia polmonare ostruttiva cronica (COPD); 11. Storia di patologie clinicamente significative cardiache (scompenso cardiaco congestizio o ipertensione severa), renali (insufficienza renale), psichiatriche (depressione o disordini dell’umore), epatiche (ittero colestatico o disfunzioni epatiche), endocrine (ipertiroidismo o soppressione surrenale) o polmonare, o anormalità nei test di laboratorio, le cui conseguenze o i cui trattamenti possano interferire con i risultati o con il trattamento del presente studio; 12. Storia di malattie psichiatriche che potrebbero richiedere il trattamento con farmaci antidepressivi durante lo studio o che abbiano richiesto il trattamento nelle due settimane precedenti; 13. Diagnosi di glaucoma o di ipertrofia prostatica; 14. Storia di abuso di alcol o droga; 15. Allergia, sensibilità o intolleranza ai farmaci di studio o ai componenti della loro formulazione (es. corticosteroidi); 16. Donne in gravidanza o in allattamento o tutte le donne fisiologicamente in grado di rimanere incinta a meno che non soddisfino la seguente definizione di post-menopausale: 12 mesi di naturale (spontaneo) amenorrea o 6 mesi di amenorrea spontanea con livelli sierici di FSH> 40 mUI / mL o che utilizzino uno o più dei seguenti metodi accettabili di contraccezione: la sterilizzazione chirurgica (per esempio la legatura bilaterale delle tube, l'isterectomia) contraccezione ormonale (impiantabile, patch, orale) metodi ai barriera doppia (qualsiasi combinazione doppia: IUD, profilattico maschile o femminile con gel spermicida, diaframma, spugna, cappuccio cervicale). Un test di gravidanza (urine) sarà effettuato al momento dello screening nelle donne in età fertile; 17. I pazienti non in grado di rispettare il protocollo o che non possano comprendere la natura, lo scopo e le possibili conseguenze dello studio; 18. Partecipazione in un altro studio nelle 12 settimane precedenti o pazienti precedentemente arruolati in questo studio.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients who will experience clinical success at 7, 14, 21 or 28 days. Clinical success is defined as a patient report of cured or much improved.

Proporzione di pazienti che mostrano il successo clinico a 7, 14, 21 o 28 giorni. Il successo clinico viene definito dal paziente che si consideri guarito o molto migliorato.

E.5.1.1

Timepoint(s) of evaluation of this end point

7, 14, 21 or 28 days.

7, 14, 21 e 28 giorni.

E.5.2

Secondary end point(s)

Time from baseline to a status of clinical success (cured or much improved); rhinosinusitis symptoms in the treatment phases; changes of overall sinus symptoms and the changes of each symptoms; level of work performance based on patient perception (recorded on a VAS scale of the diary card) and on missed working time; absence of relapses; nasal mucociliary transport time; nasal air flow resistance.

Tempo intercorso dal basale allo stato di successo clinico (guarito o molto migliorato); sintomi rinosinusali durante la fase di trattamento; variazione di tutti i sintomi sinusali e variazione di ciascun sintomo; livello della prestazione lavorativa basata sulla percezione del paziente (registrata mediante scala VAS sul diario) e tempo di assenza dal lavoro; assenza di recidive; tempo di trasporto mucociliare nasale; resistenza nasale al flusso di aria.

E.5.2.1

Timepoint(s) of evaluation of this end point

7, 14, 21 or 28 days.

7, 14, 21 e 28 giorni.

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)

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

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)

E.8.2.2

Placebo

Yes

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 end of the trial is defined as the last telephone follow-up of the last subject on the trial.

Ultima telefonata di follow up dell'utimo soggetto incluso nello studio.

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

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)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

164

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

164

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)

Not planned

Non previsti

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

2012-12-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-11-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-24

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