Aztreonam for Inhalation Solution vs Tobramycin Inhalation Solution in Patients With Cystic Fibrosis & Pseudomonas Aeruginosa

NCT00757237 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-205-0110
• Study Type: interventional
• Target: 274
• Locations: 13 countries
• Sites: 92

Brief Summary

The purpose of this study was to assess the comparative safety and effectiveness of aztreonam for inhalation solution versus tobramycin inhalation solution in adult and pediatric patients with cystic fibrosis (CF) and pulmonary Pseudomonas aeruginosa (PA) infection.

Conditions

Cystic Fibrosis

Keywords

aztreonam lysine; tobramycin inhalation solution; tobramycin nebuliser solution; cystic fibrosis; pseudomonas aeruginosa; lung infection; CFQ-R; inhaled antibiotic

Outcome Measures

Primary Outcomes (2)

• Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted at Day 28

  Spirometry was performed according to American Thoracic Society (ATS) guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the relative change from baseline in FEV1 percent predicted at Day 28 (Visit 4) was tested using an analysis of covariance (ANCOVA) model-based method.

  Baseline and end of treatment Course 1 (Day 28)

• Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses

  Spirometry was performed according to ATS guidelines at each visit. FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. Treatment effect on the average adjusted means for the actual change in FEV1 percent predicted at Visits 4, 6, and 8 (Weeks 4, 12, and 20) was tested by mixed-effect model repeated measures (MMRM) analysis using the ITT population analysis set.

  Baseline, and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20)

Secondary Outcomes (4)

• Relative Change From Baseline in FEV1 Percent Predicted at Day 28 in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization

  Baseline and end of treatment Course 1 (Day 28)

• Mean Actual Change From Baseline in FEV1 Percent Predicted Across 3 Treatment Courses in Subjects Who Received Inhaled Tobramycin for >= 84 Days in the 12 Months Prior to Randomization

  Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20)

• Time to Need for Intravenous (IV) Antipseudomonal Antibiotics for Respiratory Events

  Day 0 to Day 168 (end of study)

• Time to First Respiratory Hospitalization

  Day 0 to Day 168 (end of study)

Other Outcomes (6)

• Actual Change From Baseline in CF Questionnaire - Revised (CFQ-R) Respiratory Symptoms Scale (RSS) Score at Day 28

  Baseline and end of treatment Course 1 (Day 28)

• Mean Actual Change From Baseline in CFQ-R RSS Score Across 3 Treatment Courses

  Baseline and end of treatment Courses 1 (Week 4), 2 (Week 12), and 3 (Week 20)

• Treatment Satisfaction Questionnaire for Medication (TSQM) - Global Satisfaction Results at Week 20

  At Week 20

Study Arms (2)

AZLI 75 mg 3 times a day (TID)

EXPERIMENTAL

Drug: Aztreonam for Inhalation Solution (AZLI)

TIS 300 mg 2 times a day (BID)

ACTIVE COMPARATOR

Drug: Tobramycin Inhalation Solution (TIS)

Interventions

Aztreonam for Inhalation Solution (AZLI) DRUG

Aztreonam for inhalation solution (75 mg) was administered 3 times a day (TID) for 28 days for each treatment cycle via the PARI eFlow electronic nebulizer.

Also known as: aztreonam, AZLI, inhaled antibiotic

AZLI 75 mg 3 times a day (TID)

Tobramycin Inhalation Solution (TIS) DRUG

Tobramycin inhalation solution (300 mg) was administered 2 times a day (BID) for 28 days for each treatment cycle via the PARI LC Plus nebulizer with compressor or via another nebulizer compatible with country-specified labeling.

Also known as: tobramycin, TNS, inhaled antibiotic

TIS 300 mg 2 times a day (BID)

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females aged 6 years and older
• Subjects with CF as diagnosed by one of the following: documented sweat chloride \>= 60 mEq/L by quantitative pilocarpine iontophoresis test, or documented sweat sodium \>= 60 mmol/L, or 2 well characterized genetic mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, or abnormal nasal potential difference with accompanying symptoms characteristic of CF
• Documented PA in an expectorated sputum or throat swab culture within 3 months prior to Visit 1 or at Visit 1
• Subjects must be able to provide written informed consent/assent prior to any study related procedures; parent/guardian must be able to give written informed consent as necessary prior to any study related procedure
• Subjects must have received previous treatment with aerosolized antibiotics without demonstration of drug intolerance
• FEV1 \<= 75% predicted at Visit 1
• Ability to perform reproducible pulmonary function tests
• Chest radiograph at Visit 1 without significant acute findings (eg, infiltrates \[lobar or diffuse interstitial\], pleural effusion, pneumothorax); or chest radiograph or magnetic resonance image (MRI) obtained within the 180 days prior to Visit 1 without acute findings and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) are allowed

You may not qualify if:

• Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day
• History of sputum or throat swab culture yielding B. cepacia in the previous 2 years
• Current requirement for daily continuous oxygen supplementation or requirement for more than 2 L/minute at night
• Administration of any investigational drug or device within 28 days of Visit 1 or within 6 half-lives of the investigational drug (whichever is longer)
• Known local or systemic hypersensitivity to monobactam antibiotics
• Known allergies/intolerance to tobramycin
• Inability to tolerate inhalation of a short acting beta agonist
• Changes in or initiation of chronic azithromycin treatment within 28 days prior to Visit 1
• Administration of antipseudomonal antibiotics by inhalation, intravenous or oral routes within the 14 days prior to Randomization/Visit 2
• Changes in antimicrobial, bronchodilator (BD), dornase alfa, or corticosteroid medications within 7 days prior to Visit 1
• Changes in physiotherapy technique or schedule within 7 days prior to Visit 1
• History of lung transplantation
• Abnormal renal or hepatic function or serum chemistry at Visit 1, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 5 times upper limit of normal range (ULN) or creatinine \> 2 times ULN
• Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
• Female of childbearing potential who is lactating or is not (in the opinion of the investigator) practicing an acceptable method of birth control; female subjects who utilize hormonal contraceptives as one of their birth control methods must have used the same method for at least 3 months before study dosing

Sponsors & Collaborators

• Gilead Sciences: lead
• Chiltern International Inc.: collaborator
• ClinPhone, Inc.: collaborator
• Covance: collaborator

Study Sites (92)

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Anchorage, Alaska, 99508, United States

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Phoenix, Arizona, 85006, United States

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Tuscon, Arizona, 85724, United States

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Orange, California, 92868, United States

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Aurora, Colorado, 80045, United States

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Denver, Colorado, 80206, United States

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Wilmington, Delaware, 19803, United States

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Orlando, Florida, 32801, United States

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Tampa, Florida, 33606, United States

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Chicago, Illinois, 60637, United States

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Glenview, Illinois, 60025, United States

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Niles, Illinois, 60714, United States

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Boston, Massachusetts, 02115, United States

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Columbia, Missouri, 65212, United States

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Las Vegas, Nevada, 89107, United States

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Albany, New York, 12208, United States

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New Hyde Park, New York, 11040, United States

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Cincinnati, Ohio, 45229, United States

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Dayton, Ohio, 45404, United States

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Toledo, Ohio, 43606, United States

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Oklahoma City, Oklahoma, 73112, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19102, United States

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Philadelphia, Pennsylvania, 19104, United States

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Charleston, South Carolina, 29425, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78212, United States

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Salt Lake City, Utah, 84132, United States

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Richmond, Virginia, 23298, United States

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Innsbruck, A-6020, Austria

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Salzburg, A-5020, Austria

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Antwerp, 2650, Belgium

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Brussels, 1070, Belgium

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Brussels, 1090, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Copenhagen, DK-2100, Denmark

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Amiens, 80054, France

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Bordeaux, 33076, France

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Caen, 14000, France

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Créteil, 94000, France

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Lille, 59037, France

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Lisieux, 14100, France

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Montpellier, 34295, France

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Nice, 06202, France

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Paris, 75743, France

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Pessac, 33604, France

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Rennes, 35033, France

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Berlin, 123353, Germany

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Berlin, 13125, Germany

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Bochum, 44791, Germany

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Essen, 45122, Germany

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Essen, 45239, Germany

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Giessen, 35392, Germany

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Hamburg, 22763, Germany

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Leipzig, 04103, Germany

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Magdeburg, 39120, Germany

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Mainz, 55101, Germany

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München, 80336, Germany

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Dublin, 24, Ireland

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Dublin, 4, Ireland

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Dublin, 9, Ireland

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Dublin, Ireland

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Galway, Ireland

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Ancona, 60123, Italy

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Catania, 95123, Italy

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Milan, 20122, Italy

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Napoli, 80131, Italy

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Palermo, 90134, Italy

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Parma, 43100, Italy

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Rome, 00161, Italy

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Rome, 00165, Italy

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Verona, 37126, Italy

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Maastricht, 6229, Netherlands

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The Hague, 2504 LN, Netherlands

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Lisbon, 1649-035, Portugal

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Porto, 4200 319, Portugal

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Madrid, 28009, Spain

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Madrid, 28034, Spain

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Madrid, 28041, Spain

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Madrid, 28046, Spain

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Málaga, 29011, Spain

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Zurich, CH - 8032, Switzerland

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Zurich, CH - 8091, Switzerland

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Sheffield, West Yorkshire, S10 2TH, United Kingdom

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Belfast, BT9 7AB, United Kingdom

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Cambridge, CB23 3RE, United Kingdom

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Cardiff, CF64-2XX, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Liverpool, L14 3PE, United Kingdom

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London, SW3 6NP, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Related Publications (1)

• Assael BM, Pressler T, Bilton D, Fayon M, Fischer R, Chiron R, LaRosa M, Knoop C, McElvaney N, Lewis SA, Bresnik M, Montgomery AB, Oermann CM; AZLI Active Comparator Study Group. Inhaled aztreonam lysine vs. inhaled tobramycin in cystic fibrosis: a comparative efficacy trial. J Cyst Fibros. 2013 Mar;12(2):130-40. doi: 10.1016/j.jcf.2012.07.006. Epub 2012 Sep 15.

  PMID: 22985692 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Pseudomonas Infections

Interventions

Aztreonam; Tobramycin; 2-(4-toluidino)-6-naphthalenesulfonic acid

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Monobactams; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Mark Bresnik, MD, Director, Clinical Research
• Organization: Gilead Sciences, Inc.

mark.bresnik@gilead.com

(650) 522-5934

Study Officials

• Mark Bresnik, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 22, 2008
• First Posted: September 23, 2008
• Study Start: August 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: November 1, 2010
• Last Updated: July 4, 2011
• Results First Posted: July 4, 2011

Record last verified: 2011-06

Locations

US (29); AU (2); IT (9); NL (2); CH (2); DK (1); DE (11); GB (8); IE (5); FR (11); BE (5); PT (2); ES (5)