Clinical Trials Register

Summary
EudraCT Number:	2010-023959-28
Sponsor's Protocol Code Number:	GS-US-219-0104
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:	2012-01-24
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

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

Estudio de fase III, doble ciego, multicéntrico, aleatorizado, controlado con placebo, con el fin de evaluar tandas repetidas de aztreonam en una solución para inhalación (75 mg de aztreonam en polvo y disolvente para solución nebulizadora) en pacientes con bronquiectasias no asociadas a fibrosis quística e infección endobronquial gram-negativa (AIR-BX2)

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

Estudio de Aztreonam para inhalación frente a Placebo en pacientes con bronquiestasias y unas bacterias concretas en las vías aéreas

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	+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 Limited
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Aztreonam for Inhalation Solution
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.3.10	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 and solvent 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

bronquiectasias no asociadas a fibrosis quística e infección endobronquial gram-negativa

E.1.1.1

Medical condition in easily understood language

Bronchiectasis and specific bacteria in the airways

Bronquiectasias con unas bacterias concreas en las vías respiratorias

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	10070295
E.1.2	Term	Infective exacerbation of bronchiectasis
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	10006445
E.1.2	Term	Bronchiectasis
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal disorders

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.

Este estudio se ha diseñado para evaluar la seguridad y la eficacia de aztreonam en una solución para inhalación (75 mg de aztreonam en polvo y disolvente para solución nebulizadora) (AZLI) en pacientes con bronquiectasias no asociadas a fibrosis quística (FQ) e infección endobronquial gram-negativa.

E.2.2

Secondary objectives of the trial

Not applicable

No aplicable

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

* Varón o mujer 18 años.
* Bronquiectasias confirmadas mediante tomografía computarizada (TC) documentada en los 5 años anteriores a la visita 1, o con la aprobación del monitor médico, sin resección pulmonar intercalada.
* Expectoración crónica comunicada la mayoría de los días durante las 4 semanas anteriores a la visita 1.
* Cultivo de esputo positivo para microorganismos gram-negativos objetivo en la visita 1.
* Antecedentes documentados de cultivo de esputo positivo (o cultivo de broncoscopia) para un microorganismo gram-negativo objetivo O BIEN antecedentes documentados de tratamiento con antibióticos con cobertura de gram-negativos por una exacerbación de las bronquiectasias en los 5 años anteriores a la visita 1.
* Radiografía de tórax (RT) obtenida e interpretada en la visita 1 o entre las visitas 1 y 2, sin hallazgos agudos significativos (por ejemplo, ausencia de infiltrados nuevos). Pueden ser aceptadas RT obtenidas en los 10 días previos a la visita 1 con la aprobación previa del monitor médico.
* Volumen espiratorio forzado en el primer segundo (FEV1) 20% con respecto al valor teórico aproximadamente 15 minutos después de administrar un broncodilatador en la visita 1.

E.4

Principal exclusion criteria

* Hospitalization within 14 days prior to Visit 1
* Reported episode of hemoptysis greater than 30 mL (~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

* Hospitalización en los 14 días anteriores a la visita 1.
* Episodio comunicado de hemoptisis > 30 ml en los 14 días anteriores a la visita 1, el día de la visita 1 y entre las visitas 1 y 2.
* Antibióticos para tratar síntomas respiratorios (salvo un tratamiento estable crónico con un macrólido) en los 14 días anteriores a la visita 1, el día de la visita 1 y entre las visitas 1 y 2.
* Modificaciones de los tratamientos con broncodilatadores, corticoides inhalados, macrólidos o de higiene bronquial en los 28 días anteriores a la visita 1 y hasta la finalización del estudio.
* Modificación en la terapia sistémica con corticoides en los 28 días previos a la visita 1 y entre la visita 1 y la visita 2. Despúes de la visita 2, la terapia con corticoides sistémicos se permite (máximo 14 días) para el tratamiento del empeoramiento de signos y/o síntomas respiratorios.
* Tratamiento previo con Cayston (AZLI) o exposición previa a este producto.
* Acontecimiento adverso grave entre las visitas 1 y 2.
* Antecedentes de fibrosis quística (FQ).
* Tratamiento actual para una infección por micobacterias no tuberculosas (MNT).
* Infección activa por Mycobacterium tuberculosis (MTB) en el año anterior a la 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]).

El criterio de valoración principal será la variación de la puntuación de síntomas respiratorios de la escala QOL-B entre el período basal y el final de la tanda 1 controlada con placebo (es decir, variación entre el día 0 [visita 2] y el día 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]

Cambio desde día 0 (visita 2) hasta día 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

* Variación de la puntuación de síntomas respiratorios de la escala QOL-B al final de la tanda 2 controlada con placebo (día 84 [visita 6]) en comparación con el período basal (día 0 [visita 2]).
* Tiempo hasta una exacerbación definida por el protocolo (EDP) antes del tratamiento en régimen abierto 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]

* Cambio desde día 0 (visita 0) hasta día 84 (visita 6)
* Tiempo desde día 0 (visita 2) hasta día 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

Tratamiento abiert con PR1 en todos los pacientes despues de tramineto controlado con PL1

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

Belgium

France

Germany

Italy

Netherlands

Spain

United Kingdom

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

Date of last study visit of last study subject.

Fecha de la última visita del último paciente

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.1.1.1

In Utero