Clinical Trials Register

Summary
EudraCT Number:	2015-000395-97
Sponsor's Protocol Code Number:	GS-US-205-0117
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-02-02
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2015-000395-97

A.3

Full title of the trial

A Double-Blind, Multicenter, Multinational, Randomized, Placebo-Controlled Trial Evaluating Aztreonam Lysine for Inhalation in Patients with Cystic Fibrosis, Mild Lung Disease, and P. aeruginosa (AIR-CF4)

A.3.1

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

A Clinical Trial to Evaluate the Effects of the drug Aztreonam Lysine for Inhalation in Patients with Cystic Fibrosis, Mild Lung Disease, and infection with the bacteria Pseudomonas aeruginosa (AIR-CF4)

A.4.1

Sponsor's protocol code number

GS-US-205-0117

A.5.4

Other Identifiers

Name:

IND No

Number:

64,402

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 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, Abington
B.5.3.2	Town/ city	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
B.Sponsor: 2
B.1.1	Name of Sponsor	Gilead Sciences Pty Ltd
B.1.3.4	Country	Australia
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 Pty Ltd
B.4.2	Country	Australia
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, Abington
B.5.3.2	Town/ city	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
B.Sponsor: 3
B.1.1	Name of Sponsor	Gilead Sciences Canada, Inc.
B.1.3.4	Country	Canada
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 Canada, Inc.
B.4.2	Country	Canada
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, Abington
B.5.3.2	Town/ city	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.3.4	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.3.9.4	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 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

Cystic Fibrosis with Mild Lung Disease and P. aeruginosa (AIR-CF4)

E.1.1.1

Medical condition in easily understood language

Cystic Fibrosis with Mild Lung Disease and infection with the P. aeruginosa (AIR-CF4) bacteria.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

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

The primary objective of this study is to assess the safety and efficacy of a 28-day course of AZLI in patients with CF, mild lung disease (FEV1 > 75% predicted), and PA.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients ≥ 6 years of age.
2. Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
a. Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
b. Two well-characterized mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene; or
c. Abnormal nasal potential difference.
3. PA present in expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within the 12 months prior to Visit 1. (One of the previous PA positive cultures must be no more than 3 months prior to Visit 1.)
4. FEV1 > 75% predicted at Visit 1.
5. Patient must exhibit two or more of the following chronic and/or intermittent CF symptoms, for a minimum of 28 days prior to randomization and with no worsening of symptoms within 7 days prior to randomization:
a. Chest congestion
b. Daily cough
c. Productive cough
d. Wheezing
e. Trouble breathing
f. Nocturnal wakening due to coughing
6. Patients (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures.
7. Females of childbearing potential must have a negative urine pregnancy test at Visit 1.
8. Ability to perform reproducible pulmonary function tests.
9. In the opinion of the Investigator, the patient does not require immediate antipseudomonal antibiotic intervention to treat an impending exacerbation, and the patient’s condition is stable enough to enroll in the study.

E.4

Principal exclusion criteria

1. Administration of any investigational drug or device within 28 days prior to Visit 1 or within 6 half-lives of the investigational drug (whichever is longer).
2. Administration of any IV, oral, or inhaled antipseudomonal antibiotic within 28 days prior to Visit 1.
3. Known local or systemic hypersensitivity to monobactam antibiotics.
4. Inability to tolerate short-acting bronchodilator use at least three times daily.
5. Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1.
6. Changes in or initiation of chronic hypertonic saline treatment within 28 days prior to Visit 1.
7. Changes in or initiation of dornase alpha within 28 days prior to Visit 1.
8. Changes in antimicrobial, bronchodilator (BD), or corticosteroid medications within 7 days prior to Visit 1.
9. Changes in physiotherapy technique or schedule within 7 days prior to Visit 1.
10. History of lung transplantation.
11. History of participation (enrollment) in any prior clinical trials with AZLI.
12. A chest radiograph at Visit 1 (or within the previous 180 days of Visit 1), with abnormalities indicating a significant acute finding (e.g., lobar infiltrate and atelectasis, pneumothorax, or pleural effusion). A chest radiograph obtained and interpreted between Visits 1 and 2 is also acceptable for determining eligibility.
13. Positive urine pregnancy test at Visit 1; all women of childbearing potential will be tested.
14. Females of childbearing potential who are lactating or are not (in the opinion of the investigator) practicing an acceptable method of birth control; female patients who utilize hormonal contraceptives as their birth control method must have used the same method
for at least 3 months before study dosing.
15. Patient is being assessed at Visit 1 by the investigator for an acute change in respiratory symptoms.
16. Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is change from baseline at Day 28 in clinical symptoms as assessed by the respiratory symptoms domain of the CFQ-R.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 28

E.5.2

Secondary end point(s)

• Change from baseline in clinical symptoms as assessed by the respiratory symptoms
domain of the CFQ-R at Days 14 and 42.
• Change from baseline in clinical symptoms as assessed by the non-respiratory domains of
the CFQ-R at Day 28.
• Use of additional (non-protocol specified) antipseudomonal antibiotics during the course
of the study.
• Proportion of patients hospitalized and the number of days patients were hospitalized
during the study.
• Change from baseline in PA colony-forming units (CFUs) in sputum at Day 28.
• Relative change from baseline FEV1 percent of predicted at Day 28.

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 14, 28 and 42

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

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Australia

Canada

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.8.9.2

In all countries concerned by the trial years

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)

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)

Yes

F.1.2.1

Number of subjects for this age range:

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

157

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)

After the end of the trial patients will revert to respective standard of care.

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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