Clinical Trials Register

Summary
EudraCT Number:	2011-001362-18
Sponsor's Protocol Code Number:	GS-US-205-0160
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:	2012-02-22
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

2011-001362-18

A.3

Full title of the trial

Open-Label Phase 3 Trial to Evaluate the Safety of Aztreonam 75 mg Powder and Solvent for Nebuliser Solution/Aztreonam for Inhalation Solution (AZLI) in Children with Cystic Fibrosis (CF) and Chronic Pseudomonas aeruginosa (PA) in the Lower Airways.

Studio in aperto di fase 3 finalizzato alla valutazione della sicurezza di aztreonam 75 mg polvere e solvente per soluzione per nebulizzatore/aztreonam per soluzione per inalazione (AZLI) in soggetti in eta' pediatrica affetti da fibrosi cistica (FC) e infezione cronica da pseudomonas aeruginosa (PA) alle vie aeree inferiori.

A.3.1

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

Study of the Safety of Aztreonam for Inhalation in Children with Cystic Fibrosis and Chronic Infection of the Airways by Pseudomonas aeruginosa bacteria.

Studio per valutare la sicurezza di aztreonam per inalazione in bambini con fibrosi cistica ed infezione cronica delle vie aeree da batterio Pseudomonas aeruginosa.

A.3.2

Name or abbreviated title of the trial where available

PALS (Pediatric Aztreonam Lysine Safety)

A.4.1

Sponsor's protocol code number

GS-US-205-0160

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01404234

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/117/2011

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 Ltd
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 Ltd
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/04/204
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	NA
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Cystic fibrosis and chronic infection of lower respiratory tract with Pseudomonas aeruginosa.

Fibrosi cistica ed infezione cronica delle basse vie respiratorie dovuta a Pseudomonas aeruginosa.

E.1.1.1

Medical condition in easily understood language

Cystic fibrosis and chronic lung infection with a bacterium (germ) called Pseudomonas aeruginosa.

Fibrosi cistica ed infezione cronica polmonare causata da un batterio (germe) chiamato Pseudomonas aeruginosa.

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	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.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10056971
E.1.2	Term	Infective exacerbation of chronic obstructive airways disease
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate safety of treatment with AZLI 75 mg 3 times daily (TID) for 3 courses of therapy (28 days on/28 days off) in female and male children less than 13 years of age with CF and chronic PA infection/colonization.

Valutare la sicurezza del trattamento con AZLI 75 mg 3 volte al giorno (TID) per 3 cicli di terapia (28 giorni di trattamento/28 giorni senza trattamento) in soggetti in età pediatrica di sesso femminile e maschile di età inferiore a 13 anni affetti da FC ed infezione/colonizzazione cronica da PA.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Aged 12 years or less. - Diagnosis of CF as determined by the 1997 CF Consensus Conference criteria: sweat chloride level ≥ 60 mEq/L by quantitative pilocarpine iontophoresis; or a genotype with 2 identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference (NPD), and 1 or more clinical features consistent with CF. -Documented positive lower respiratory tract culture for PA at the screening visit plus 2 documented positive lower respiratory tract cultures for PA within 12 months prior to study entry (start of treatment). -Clinically stable with no evidence of significant respiratory symptoms or, if obtained for clinical evaluation, no chest radiograph findings at screening that would require administration of IV antipseudomonal antibiotics, oxygen supplementation, or hospitalization.

-Età inferiore o pari a 12 anni. -Diagnosi di FC come stabilito in base ai criteri della Consensus Conference sulla fibrosi cistica del 1997: livello di cloruro nel sudore ≥ 60 mEq/L per ionoforesi pilocarpinica quantitativa; oppure un genotipo con due mutazioni identificabili in linea con la diagnosi di FC; oppure un'anomala differenza di potenziali transepiteliali della mucosa nasale (NPD) e 1 o più fattori clinici in linea con la diagnosi di FC. -Coltura positiva documentata del tratto respiratorio inferiore per la PA alla visita di screening oltre a 2 colture positive documentate del tratto respiratorio inferiore per la PA nei dodici mesi antecedenti all'ingresso nello studio (inizio del trattamento). -Stabilità clinica senza prova di sintomi respiratori significativi oppure, se effettuata ai fini della valutazione clinica, assenza di esiti alla radiografia toracica in sede di screening che richiederebbero la somministrazione di antibiotici anti-Pseudomonas e.v., supplementazione di ossigeno o ricovero ospedaliero.

E.4

Principal exclusion criteria

- Use of IV or inhaled antipseudomonal antibiotics within 14 days of study entry (start of treatment). - Presence of a condition or abnormality that would compromise the participant’s safety or the quality of study data, in the opinion of the investigator. - History of hypersensitivity/adverse reaction to aztreonam or beta-agonists. - Use of any investigational drug within 30 days of study entry (start of treatment).

- Uso di antibiotici anti-pseudomonas e.v. o per inalazione nei 14 giorni antecedenti all'ingresso nello studio (inizio del trattamento). - Presenza di una condizione o anomalia che comprometterebbe la sicurezza del partecipante o la qualità dei dati relativi allo studio, a parere dello sperimentatore. - Storia di ipersensibilità/reazione avversa ad aztreonam o a beta-antagonisti. - Assunzione di un qualsiasi farmaco sperimentale nei 30 giorni antecedenti all'ingresso nello studio (inizio del trattamento).

E.5 End points

E.5.1

Primary end point(s)

Percentage of subjects who have discontinued the study drug due to safety or tolerability reasons by Day 168.

Valutare la percentuale di pazienti che hanno interrotto la somministrazione del farmaco in studio per motivi legati alla sicurezza o alla tollerabilità entro il giorno 168.

E.5.1.1

Timepoint(s) of evaluation of this end point

Between baseline (Day 1) and Day 168.

Dalla visita basale (giorno 1) al giorno 168.

E.5.2

Secondary end point(s)

For subjects aged 6 years or more: - Change in FEV1 % predicted at end of each 28-day-on-treatment cycle of AZLI; - Change in CFQ-R respiratory symptoms scale (RSS) score at the end of each 28-day-on-treatment cycle of AZLI. For all subjects: - Change in PA sputum density at end of each 28-day-on-treatment cycle of AZLI; -Use of additional antipseudomonal antibiotics; -Number and duration of hospitalizations; -Number and time to PA exacerbations; -Study-drug induced bronchospasm; -Adverse event rates adjusted for study duration.

Per i soggetti di età superiore o pari a 6 anni: -variazione della FEV1% alla fine di ogni ciclo di trattamento di 28 giorni con AZLI; -variazioni del punteggio nella scala dei sintomi respiratori del CFQ-R (respiratory symptoms scale, RSS) al termine di ogni ciclo di trattamento di 28 giorni con AZLI. Per tutti i soggetti: -variazone della densità dell'espettorato PA al termine di ogni ciclo di trattamento di 28 giorni con AZLI; -assunzione di altri antibiotici antipseudomonas; -numero e durata dei ricoveri ospedalieri; -numero e tempo tra le riacutizzazioni della PA; -broncospasmo indotto dal farmaco in studio; -tassi degli eventi avversi corretti in base alla durata dello studio.

E.5.2.1

Timepoint(s) of evaluation of this end point

For subjects aged 6 years or more at Days 28, 84, and 140: - Change from baseline in FEV1 % predicted; - Change from baseline in CFQ-R respiratory symptoms scale (RSS) score. For all subjects at Days 28, 84 and 140: - Change from baseline in PA sputum density. For all subjects from baseline to end of treatment (Day 140): - Study-drug induced bronchospasm For all subjects from screening to end of study (Day 168): - Use of additional antipseudomonal antibiotics; - Number and duration of hospitalizations; - Number and time to PA exacerbations; - Adverse event rates adjusted for study duration.

Per i soggetti di età superiore o pari a 6 anni ai giorni 28, 84 e 140: - variazione della FEV1% rispetto al basale; - variazioni del punteggio nella scala dei sintomi respiratori del CFQ-R (respiratory symptoms scale, RSS) rispetto al basale. Per tutti i soggetti ai giorni 28,84 e 140: - variazone della densità dell'espettorato PA rispetto al basale. Per tutti i soggetti dal basale alla fine del trattamento (giorno 140): - broncospasmo indotto dal farmaco in studio. Per tutti i soggetti dallo screening alla fine dello studio (giorno 168): -assunzione di altri antibiotici antipseudomonas; -numero e durata dei ricoveri ospedalieri; -numero e tempo tra le riacutizzazioni della PA; -tassi degli eventi avversi corretti in base alla durata dello studio.

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

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

E.8.1.1

Randomised

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

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

Yes

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Infants and young children

Lattanti e bambini

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Adolescent girls of childbearing potential using contraception.

Ragazze adolescenti in età fertile che fanno uso di contraccettivi.

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

F.4.2.2

In the whole clinical trial

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 dovranno fare riferimento al medico per il proseguimento del trattamento.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Cystic Fibrosis Foundation Therapeutics (CFFT)
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	European Cystic Fibrosis Society Clinical Trials Network (ECFS-CTN)

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-02-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-04-03

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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