Clinical Trials Register

Summary
EudraCT Number:	2010-023959-28
Sponsor's Protocol Code Number:	GS-US-219-0104
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:	2012-03-07
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

2010-023959-28

A.3

Full title of the trial

A Phase 3, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Evaluating Repeated Courses of Aztreonam for Inhalation Solution/Aztreonam 75 mg Powder and Solvent for Nebuliser Solution in Subjects with non-CF Bronchiectasis and Gram-Negative Endobronchial Infection.

Studio di Fase 3, in doppio cieco, multicentrico, randomizzato, controllato con placebo per la valutazione di cicli ripetuti di Aztreonam soluzione per inalazione/Aztreonam 75 mg polvere e solvente per soluzione per nebulizzatore in soggetti con bronchiectasia non fibrocistica ed infezione endobronchiale da gram-negativi.

A.3.1

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

Study of Aztreonam for Inhalation Versus Placebo in Patients with Bronchiectasis and Specific Bacteria in the Airways

Studio con aztrenam per inalazione verso placebo in soggetti con bronchiectasia e batteri specifici nelle vie aeree.

A.3.2

Name or abbreviated title of the trial where available

AIR-BX2

A.4.1

Sponsor's protocol code number

GS-US-219-0104

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01314716

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	GILEAD SCIENCES INC.
B.1.3.4	Country	United States
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	Gilead Sciences, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Gilead Sciences International Limited
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Flowers Building, Granta Park
B.5.3.2	Town/ city	Abington, Cambridge
B.5.3.3	Post code	CB21 6GT
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1223 897496
B.5.5	Fax number	+44 1223 897284
B.5.6	E-mail	clinical.trials@gilead.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	Cayston - Aztreonam 75 mg powder and solvent for nebuliser solution
D.2.1.1.2	Name of the Marketing Authorisation holder	Gilead Sciences International Limited
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	Powder for nebuliser 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	AZTREONAM
D.3.9.1	CAS number	78110-38-0
D.3.9.2	Current sponsor code	AZLI
D.3.9.3	Other descriptive name	NA
D.3.9.4	EV Substance Code	SUB05664MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	75
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	Powder for 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

Non-CF bronchiectasis and gram-negative endobronchial infection

Bronchiectasia non fibrocistica ed infezione endobronchiale gram-negativa

E.1.1.1

Medical condition in easily understood language

Bronchiectasis and specific bacteria infection in the airways

Bronchiectasia e infezione da batteri specifici nelle vie aeree

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	PT
E.1.2	Classification code	10006445
E.1.2	Term	Bronchiectasis
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	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10021881
E.1.2	Term	Infections and infestations
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

This study is designed to assess the safety and efficacy of aztreonam for inhalation solution/aztreonam 75 mg powder and solvent for nebuliser solution (AZLI) in subjects with non-CF bronchiectasis and gram negative endobronchial infection.

Questo studio intende valutare la sicurezza e l’efficacia di aztreonam soluzione per inalazione/aztreonam 75 mg polvere e solvente per soluzione per nebulizzatore (AZLI) in soggetti con bronchiectasia non fibrocistica ed infezione endobronchiale gram-negativa.

E.2.2

Secondary objectives of the trial

Not applicable

Non applicabile

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male/Female not less than 18 years old; • Bronchiectasis confirmed by documented computed tomography (CT) scan within 5 years prior to Visit 1, or by prior approval of the Medical Monitor without intervening lung resection; • Reported chronic sputum production on most days during the 4 weeks prior to Visit 1; • Positive sputum culture for target gram-negative organism(s) at Visit 1; • Documented history of positive sputum culture (or bronchoscopic culture) for a target gram-negative organism OR documented history of treatment with antibiotics with gram-negative coverage for an exacerbation of bronchiectasis within 5 years prior to Visit 1; • Chest X-Ray (CXR) obtained and interpreted at Visit 1 or between Visits 1 and 2, without significant acute findings (e.g., no new infiltrate). With prior approval of the Medical Monitor, a CXR obtained within 10 days prior to Visit 1 may be acceptable for study entry. • Forced expiratory volume in one second (FEV1) not less than 20% predicted approximately 15 minutes post-bronchodilator at Visit 1.

• Maschio/Femmina ≥ 18 anni; • Bronchiectasia confermata da tomografia computerizzata (TAC) documentata nei 5 anni precedenti alla Visita 1, o da approvazione del medical monitor, senza intervento di resezione polmonare; • Riportata produzione di espettorato almeno 4 volte al giorno durante le 4 settimane precedenti alla Visita 1; • Positivita' all’esame colturale dell’espettorato per l’organismo (o gli organismi) gram-negativo/i bersaglio alla Visita 1; • Anamnesi documentata di positivita' della coltura dell’espettorato (o della coltura broncoscopica) per un organismo bersaglio gram-negativo OPPURE anamnesi documentata di trattamento con antibiotici con copertura per i gram-negativi per una esacerbazione di bronchiectasia nei 5 anni precedenti alla Visita 1; • Radiografia del torace (CXR) ottenuta ed interpretata in Visita 1 o tra le Visite 1 e 2, senza riscontri acuti significativi (ad es., nessun nuovo infiltrato). Tramite previa approvazione del medical monitor, un CXR ottenuto entro i 10 giorni precedenti la Visita 1, puo' essere considerato valido per la partecipazione allo studio. • Volume espiratorio forzato in un secondo (FEV1) ≥ 20% del previsto circa 15 minuti dopo l’uso del broncodilatatore alla Visita 1.

E.4

Principal exclusion criteria

• Hospitalization within 14 days prior to Visit 1; • Reported episode of hemoptysis greater than 30 mL (about 2 tablespoons) within 14 days prior to Visit 1, on the day of Visit 1, and from Visit 1 through Visit 2; • Antibiotics to treat respiratory symptoms (excluding chronic, stable treatment with a macrolide) within 14 days prior to Visit 1, on the day of Visit 1, and from Visit 1 through Visit 2; • Change in bronchodilator, inhaled corticosteroid, macrolide, or bronchial hygiene therapies within 28 days prior to Visit 1 and through study completion; • Change in systemic corticosteroid therapy within 28 days prior to Visit 1 and from Visit 1 through Visit 2. After Visit 2, systemic corticosteroid therapy (maximum of 14 days per course) will be allowed to treat worsening respiratory signs and/or symptoms; •Previous treatment with or exposure to Cayston (AZLI); • Serious adverse event between Visits 1 and 2; • History of cystic fibrosis (CF); • Current treatment for nontuberculous mycobacteria (NTM) infection; • Active mycobacterium tuberculosis (MTB) infection within one year prior to Visit 1.

• Ospedalizzazione nei 14 giorni precedenti alla Visita 1; • Episodio di emottisi > 30 ml (circa 2 cucchiai) nei 14 giorni prima della Visita 1, il giorno della Visita 1, e tra la Visita 1 e la Visita 2; • Antibiotici per il trattamento dei sintomi respiratori (escluso il trattamento cronico e stabile con macrolide) nei 14 giorni prima della Visita 1 nel giorno della Visita 1, e tra la Visita 1 e la Visita 2; • Cambiamenti nell’uso di broncodilatatori, corticosteroidi per inalazione, macrolidi, o terapie di igiene bronchiale nei 28 giorni prima della Visita 1 e fino al completamento dello studio; • Cambiamenti nella terapia sistemica con corticosteroidi nei 28 giorni precedenti la Visita 1 e dalla Visita 1 fino alla Visita 2. Dopo la Visita 2, sara' consentita la terapia sistemica con corticosteroidi (un massimo di 14 giorni per ciclo) per trattare segni e/o sintomi di peggioramento respiratorio. • Trattamento precedente con o esposizione a Cayston (AZLI); • Evento avverso grave tra le Visite 1 e 2; • Anamnesi di fibrosi cistica (FC); • Trattamento in corso per infezione da micobatteri non tubercolotici (NTM); • Infezione attiva da micobatterio della tubercolosi (MTB) entro un anno prima della Visita 1.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the change in the Respiratory Symptoms score on the QOL-B from baseline to the end of placebo-controlled Course 1 (i.e., change from Day 0 [Visit 2] to Day 28 [Visit 4]).

L’endpoint primario e' la variazione nel punteggio dei sintomi respiratori al QOL-B dal basale alla fine del Ciclo 1 controllato con placebo (cioe', variazione dal Giorno 0 [Visita 2] al Giorno 28 [Visita 4]).

E.5.1.1

Timepoint(s) of evaluation of this end point

Change from Day 0 [Visit 2] to Day 28 [Visit 4].

Variazione dal Giorno 0 [Visita 2] al Giorno 28 [Visita 4].

E.5.2

Secondary end point(s)

• Change in the Respiratory Symptoms score on the QOL-B at the end of placebo-controlled Course 2 (Day 84 [Visit 6]) compared to baseline (Day 0 [Visit 2]); • Time to Protocol-Defined Exacerbation (PDE) prior to open label AZLI treatment.

• Variazione nel punteggio dei sintomi respiratori sul QOL-B dal basale alla fine del Ciclo 2 controllato con placebo (Giorno 84 [Visita 6]) rispetto al basale (Giorno 0 [Visita 2]); • Tempo alla Esacerbazione come definita dal protocollo (PDE) prima del trattamento in aperto con AZLI.

E.5.2.1

Timepoint(s) of evaluation of this end point

•Change from Day 0 [Visit 2] to Day 84 [Visit 6]; • Entire time from Day 0 [Visit 2] to Day 112 [Visit 7].

•Variazione dal Giorno 0 [Visita 2] al Giorno 84 [Visita 6]. •Tutta la durata dal Giorno 0 [Visita 2] al Giorno 112 [Visita 7].

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)

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

Yes

E.8.1.7.1

Other trial design description

Fase in aperto del medicinale in studio per tutti i pazienti dopo la fase controllata vs placebo.

Open label course of study drug for all subjects after the placebo-controlled courses

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

United States

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

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

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

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:

150

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.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

172

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)

Upon completion of study participation, subjects will be referred back to the physician who referred them to the study for continuing care and treatment.

Al termine della partecipazione allo studio i soggetti verranno informati dal medico in merito al proseguimento delle cure e del trattamento.

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

2011-09-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-16

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