Clinical Trials Register

Summary
EudraCT Number:	2011-001362-18
Sponsor's Protocol Code Number:	GS-US-205-0160
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-21
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

Spain - AEMPS

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

Estudio abierto en fase 3 para evaluar la seguridad de aztreonam 75 mg en polvo y disolvente para solución para inhalación por nebulizador / aztreonam para solución para inhalación (AZLI) en niños con fibrosis quística (FQ) e infección crónica por Pseudomonas aeruginosa (PA) en las vías respiratorias bajas.

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

Estudio de seguridad del aztreonam inhalado en niños/as con fibrosis quística e infección crónica por la la bacteria Pseudomonas Aeruginosa en las vías respiratorias.

A.3.2

Name or abbreviated title of the trial where available

PALS (Pediatric Aztreonam Lysine Safety)

PALS (Seguridad pediátrica del aztreonam lisina)

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	+441223897496
B.5.5	Fax number	+441223897284
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
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.1	Product name	Aztreonam solución para inhalación
D.3.2	Product code	AZLI
D.3.4	Pharmaceutical form	Powder and solvent 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	N/A
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

Fibrosis quística e infección crónica de las vías respiratorias bajas por 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

Fibrosis quística e infección crónica pulmonar por la bacteria llamada
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	LLT
E.1.2	Classification code	10068288
E.1.2	Term	Cystic fibrosis pulmonary exacerbation
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	10070608
E.1.2	Term	Infective pulmonary exacerbation of cystic fibrosis
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

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.

Evaluar la seguridad del tratamiento con 3 dosis diarias (TID) de 75 mg de AZLI durante 3 ciclos de tratamiento (28 días de tratamiento / 28 días de reposo) en niños y niñas de menos de 13 años con FQ e infección / colonización crónica por PA.

E.2.2

Secondary objectives of the trial

N/A

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.

? Niños o niñas con una edad máxima de 12 años.
? Diagnóstico de FQ determinado según los criterios de la Conferencia de Consenso sobre la Fibrosis Quística de 1997: Cloruro en el sudor ? 60 mEq/l en la prueba cuantitativa de iontoforesis con pilocarpina; o prueba anómala de la diferencia de potencial nasal transepitelial (NPD); o genotipo con 2 mutaciones identificables coherentes con un diagnóstico de FQ; y 1 o más de los rasgos clínicos coherentes con la FQ.
? Cultivo de las vías respiratorias bajas documentado como positivo para PA en la visita de selección más otros 2 cultivos documentados como positivos durante los 12 meses anteriores a la inclusión en el estudio.
? Clínicamente estable y sin signos de síntomas respiratorios importantes o, si se obtiene para una evaluación clínica, ausencia de hallazgos radiológicos en la selección que requiriesen la administración de antibióticos i.v. contra Pseudomonas, suplementación de oxígeno u hospitalización.

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 de antibióticos contra Pseudomonas inhalados o por vía intravenosa en los 14 días previos a la incorporación al estudio (inicio del tratamiento).
? Presencia de una afección o anomalía que, en opinión del investigador, ponga en peligro la seguridad del participante o la calidad de los datos del estudio.
? Historia de hipersensibilidad / reacción adversa al aztreonam o a los agonistas beta.
? Uso de cualquier fármaco en investigación durante los 30 días anteriores a la entrada en el estudio (inicio del tratamiento).

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.

Porcentaje de sujetos al día 168 que hayan abandonado el tratamiento del estudio por motivos de seguridad o de tolerabilidad.

E.5.1.1

Timepoint(s) of evaluation of this end point

Between baseline (Day 1) and Day 168.

Entre el comienzo del tratamiento (Día 1) y el día 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

En pacientes ? 6 años de edad:
? Cambio en el VEF1 % estimado al final de cada ciclo de 28 días de tratamiento con AZLI.
? Cambio en la escala de síntomas (ESR) respiratorios del CFQ-R al final de cada ciclo de 28 días de tratamiento con AZLI.
En todos los pacientes:
? Cambio en la densidad de PA en el esputo al final de cada ciclo de 28 días de tratamiento con AZLI.
? Utilización de antibióticos adicionales contra Pseudomonas.
? Número y duración de las hospitalizaciones.
? Número y tiempo transcurrido hasta las exacerbaciones de PA.
? Broncoespasmo inducido por el fármaco del estudio.
? Tasas de acontecimientos adversos ajustadas según la duración del estudio.

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

En pacientes ? 6 años (días 28, 84 y 140):
? Cambio respecto al nivel inicial en el % predicho del VEF1
? Cambio respecto al nivel inicial en la puntuación en la escala de síntomas respiratorios de la CFQ-R.
En todos los pacientes (días 28, 84 y 140):
? Cambio en la densidad de PA en el esputo
En todos los pacientes desde el día 1 hasta el fin del tratamiento (día 140):
? Broncoespasmo inducido por el fármaco del estudio.
En todos los pacientes desde la selección hasta el fin del estudio (día 168):
? Utilización de antibióticos adicionales contra Pseudomonas.
? Número y duración de las hospitalizaciones.
? Número y tiempo transcurrido hasta las exacerbaciones de PA.
? Tasas de acontecimientos adversos ajustadas según la duración del estudio.

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

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

France

Germany

Italy

Poland

Spain

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

Bebés y niños.

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Adolescent girls of childbearing potential using contraception

Chicas adolescentes potencialmente fértiles usando métodos anticonceptivos

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 final de su participación en el estudio, los sujetos serán referidos de nuevo al médico que les recomendó el estudio para continuar con su cuidado y tratamiento.

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) Therapeutics Development Network (TDN)
G.4.3.4	Network Country	United States
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)
G.4.3.4	Network Country	Denmark

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-01-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-01-09

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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