Study Evaluating Fosfomycin/Tobramycin for Inhalation in Cystic Fibrosis Patients With Pseudomonas Aeruginosa Lung Infection

NCT00794586 | Completed Phase 2 DMC

• 1 other identifier: GS-US-207-0103
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 36

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of 2 dose combinations of fosfomycin/tobramycin for inhalation (FTI), following a 28-day course of Aztreonam for Inhalation (AZLI) in patients with cystic fibrosis and Pseudomonas aeruginosa lung infection.

Conditions

Cystic Fibrosis

Keywords

cystic fibrosis; CF; inhaled antibiotic; antipseudomonal antibiotic; tobramycin; fosfomycin; lung infection; pseudomonal infection; FTI

Outcome Measures

Primary Outcomes (1)

• Relative change in lung function from baseline at Day 28.

  28 Days

Study Arms (4)

FTI 80mg/20mg BID

EXPERIMENTAL

Fosfomycin/Tobramycin combination 80mg/20 mg inhaled twice daily

Drug: FTI, AZLI

FTI 160mg/40mg BID

EXPERIMENTAL

Fosfomycin/Tobramycin combination 160 mg/40 mg inhaled twice daily

Drug: FTI, AZLI

Placebo A BID

PLACEBO COMPARATOR

Placebo A inhaled twice daily

Drug: Placebo, AZLI

Placebo B BID

PLACEBO COMPARATOR

Placebo B inhaled twice daily

Drug: Placebo, AZLI

Interventions

FTI, AZLI DRUG

Evaluation of 2 dosage combinations of fosfomycin and tobramycin inhaled twice daily for 28 days following 28 days of inhaled AZLI (Aztreonam Lysine for Inhalation)

FTI 160mg/40mg BID; FTI 80mg/20mg BID

Placebo, AZLI DRUG

Volume-matched placebo inhaled twice daily for 28 days following 28 days of AZLI (Aztreonam Lysine for Inhalation).

Placebo A BID; Placebo B BID

Eligibility Criteria

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

You may qualify if:

• Males or females aged 18 years and older
• Patients with CF as diagnosed by one of the following:
• Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test, OR
• Documented sweat sodium greater than or equal to 60 mmol/L, OR
• Abnormal nasal potential difference, OR
• Two well-characterized genetic mutations in the CF transmembrane conductance regulator (CFTR) gene, AND
• Accompanying symptoms characteristic of CF
• Documented presence of PA in an expectorated sputum or throat swab culture at Visit 1 OR documented PA in 2 expectorated sputum or throat swab cultures within 12 months prior to Visit 1; one of the previous PA-positive cultures must be within 3 months prior to Visit 1
• Patients must be able to provide written informed consent prior to any study related procedures
• FEV1 greater than or equal to 25% and less than or equal to 75% predicted at Visit 1
• Ability to perform reproducible pulmonary function tests
• Chest radiograph at Visit 1 without significant acute findings (e.g., infiltrates \[lobar or diffuse interstitial\], pleural effusion, pneumothorax); or chest radiograph, CT, or MRI obtained within the 90 days prior to Visit 1 without acute findings or significant intercurrent illness; chronic, stable findings (e.g., 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 or other aminoglycosides
• Known allergies/intolerance to fosfomycin
• Inability to tolerate inhalation of a short acting beta2 agonist
• Changes in or initiation of chronic azithromycin treatment within 14 days prior to Visit 1
• Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes within the 14 days prior to Visit 1
• Changes in antimicrobial, bronchodilator (BD), corticosteroid, hypertonic saline, or dornase alfa 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:
• AST, ALT \> 3 times upper limit of normal range (ULN)

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (36)

Unknown Facility

Anchorage, Alaska, 99508, United States

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Phoenix, Arizona, 85016, United States

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Tucson, Arizona, 85724, United States

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Little Rock, Arkansas, 72205, United States

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Palo Alto, California, 94304, United States

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Denver, Colorado, 80206, United States

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Hartford, Connecticut, 06102, United States

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New Haven, Connecticut, 06520, United States

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Washington D.C., District of Columbia, 20010, United States

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Orlando, Florida, 32803, United States

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Tampa, Florida, 33606, United States

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Chicago, Illinois, 60614, United States

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Glenview, Illinois, 60025, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48201, 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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Buffalo, New York, 14222, United States

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New Hyde Park, New York, 11040, United States

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New York, New York, 10032, United States

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Syracuse, New York, 13210, United States

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Chapel Hill, North Carolina, 27599, United States

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Cincinnati, Ohio, 45229, United States

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Cleveland, Ohio, 44106, United States

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Columbus, Ohio, 43205, 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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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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Portsmouth, Virginia, 23708, United States

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Richmond, Virginia, 23298, United States

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Tacoma, Washington, 98405, United States

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MeSH Terms

Conditions

Cystic Fibrosis

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

Study Officials

• Bruce Trapnell, MD

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2008
• First Posted: November 20, 2008
• Study Start: November 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: December 27, 2013

Record last verified: 2013-12

Locations

US (36)