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

• ClinicalTrials.gov Identifier: NCT00794586
• Recruitment Status: Completed
• First Posted: November 20, 2008
• Last Update Posted: December 27, 2013
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: FTI, AZLI; Drug: Placebo, AZLI	Phase 2

Detailed Description:

Gilead is developing a broad spectrum combination antibiotic (FTI) consisting of fosfomycin (an antibiotic with activity against gram-positive and gram-negative bacteria) and tobramycin (an aminoglycoside antibiotic with potent gram-negative activity) for treatment of patients with CF. FTI offers a potential option for treatment of CF lung infections. It is important to note that the concentration of tobramycin in FTI is lower than that of the approved dose of inhaled tobramycin alone, thereby demonstrating the potential of FTI to minimize long-term toxicity from repeated exposure to aminoglycosides like tobramycin. This study will 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Double-Blind, Multicenter, Randomized, Placebo-Controlled Trial Evaluating Fosfomycin/Tobramycin for Inhalation in Patients With Cystic Fibrosis and Pseudomonas Aeruginosa
• Study Start Date: November 2008
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: FTI 80mg/20mg BID; Fosfomycin/Tobramycin combination 80mg/20 mg inhaled twice daily	Drug: FTI, AZLI; 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)
Experimental: FTI 160mg/40mg BID; Fosfomycin/Tobramycin combination 160 mg/40 mg inhaled twice daily	Drug: FTI, AZLI; 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)
Placebo Comparator: Placebo A BID; Placebo A inhaled twice daily	Drug: Placebo, AZLI; Volume-matched placebo inhaled twice daily for 28 days following 28 days of AZLI (Aztreonam Lysine for Inhalation).
Placebo Comparator: Placebo B BID; Placebo B inhaled twice daily	Drug: Placebo, AZLI; Volume-matched placebo inhaled twice daily for 28 days following 28 days of AZLI (Aztreonam Lysine for Inhalation).

Outcome Measures

Primary Outcome Measures :

1. Relative change in lung function from baseline at Day 28. [ Time Frame: 28 Days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)
  • Creatinine > 1.5 times ULN
• Positive pregnancy test at Visit 1; all women of childbearing potential will be tested
• Female patients 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 a birth control method must have used the same method for at least 3 months before study dosing
• 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

Contacts and Locations

Locations

United States, Alaska

Anchorage, Alaska, United States, 99508

United States, Arizona

Phoenix, Arizona, United States, 85016

Tucson, Arizona, United States, 85724

United States, Arkansas

Little Rock, Arkansas, United States, 72205

United States, California

Palo Alto, California, United States, 94304

United States, Colorado

Denver, Colorado, United States, 80206

United States, Connecticut

Hartford, Connecticut, United States, 06102

New Haven, Connecticut, United States, 06520

United States, District of Columbia

Washington, District of Columbia, United States, 20010

United States, Florida

Orlando, Florida, United States, 32803

Tampa, Florida, United States, 33606

United States, Illinois

Chicago, Illinois, United States, 60614

Glenview, Illinois, United States, 60025

United States, Massachusetts

Boston, Massachusetts, United States, 02114

Boston, Massachusetts, United States, 02115

United States, Michigan

Ann Arbor, Michigan, United States, 48109

Detroit, Michigan, United States, 48201

United States, Nevada

Las Vegas, Nevada, United States, 89107

United States, New York

Albany, New York, United States, 12208

Buffalo, New York, United States, 14222

New Hyde Park, New York, United States, 11040

New York, New York, United States, 10032

Syracuse, New York, United States, 13210

United States, North Carolina

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Cincinnati, Ohio, United States, 45229

Cleveland, Ohio, United States, 44106

Columbus, Ohio, United States, 43205

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73112

United States, Pennsylvania

Hershey, Pennsylvania, United States, 17033

Philadelphia, Pennsylvania, United States, 19102

United States, South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

Houston, Texas, United States, 77030

San Antonio, Texas, United States, 78212

United States, Virginia

Portsmouth, Virginia, United States, 23708

Richmond, Virginia, United States, 23298

United States, Washington

Tacoma, Washington, United States, 98405

Sponsors and Collaborators

Gilead Sciences

Investigators

• Principal Investigator: Bruce Trapnell, MD; Children's Hospital Medical Center, Cincinnati

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT00794586
• Other Study ID Numbers: GS-US-207-0103
• First Posted: November 20, 2008
• Last Update Posted: December 27, 2013
• Last Verified: December 2013

Keywords provided by Gilead Sciences:

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

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases