Clinical trial NCT00794586: Study Evaluating Fosfomycin/Tobramycin for Inhalation in Cystic Fibrosis Patients With Pseudomonas Aeruginosa Lung Infection
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: cystic fibrosis
CF
inhaled antibiotic
antipseudomonal antibiotic
tobramycin
fosfomycin
lung infection
pseudomonal infection
FTI
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2008-11-20
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Relative change in lung function from baseline at Day 28.
timeFrame: 28 Days
Secondary outcomes:
Other outcomes:
Locations:
city: Anchorage
country: United States
state: Alaska
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Palo Alto
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Washington
country: United States
state: District of Columbia
city: Orlando
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Glenview
country: United States
state: Illinois
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Albany
country: United States
state: New York
city: Buffalo
country: United States
state: New York
city: New Hyde Park
country: United States
state: New York
city: New York
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Portsmouth
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Tacoma
country: United States
state: Washington
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Bruce Trapnell, MD
role: PRINCIPAL_INVESTIGATOR
References: