Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Safety and Efficacy Study of Aztreonam for Inhalation Solution (AZLI) in Patients With Cystic Fibrosis and Chronic Burkholderia Species Infection

Sponsor: Gilead Sciences


The purpose of this research study is to see if an experimental drug called Aztreonam for Inhalation Solution is safe and effective to treat Burkholderia lung infections in patients with Cystic fibrosis.

Drug: Aztreonam for Inhalation solution

Study Type: Phase III

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Official Title:
Phase 3b Randomized, Double-Blind, Placebo-Controlled Two-Part Trail to Assess the Safety and Efficacy of Continuous Aztreonam for Inhalation Solution (AZLI) in Subjects With Cystic Fibrosis(CF) and Chronic Burkholderia Species Infection

Primary Outcome Measures:
Change from baseline in FEV1 percent predicted as measured by the AUCave through week 24.

Secondary Outcome Measures:
AUCave of relative change from baseline in FEV1, FVC, and FEF25 to 75 percent through week 24.

Estimated Enrollment:
76

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.
lactose and sodium chloride: Placebo Comparator

Aztreonam for inhalation solution(75mg)will be administered three times a day, with at least 4 hours between doses, for up 48 hours via the PARI investigational eFlow electronic nebulizer.

Eligibility

Ages Eligible for Study:
6 Years and older

Inclusion Criteria:
Male or female ≥ 6 years of age

Subjects with CF as diagnosed by one of the following:
Documented sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis test
Documented sweat sodium ≥ 60 mmol/L
Two well characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
Abnormal NPD with accompanying symptoms characteristic of CF

Chronic infection with Burkholderia spp. defined by:
One sputum culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
At least 50% of sputum cultures collected at least one month apart over the previous 12 months prior to baseline assessment positive for Burkholderia spp. (minimum of 2 positive cultures), and
At least one positive sputum culture (obtained at any point in time) confirmed to be Burkholderia spp. by the CFF Burkholderia cepacia Research Laboratory and Repository at the University of Michigan (or equivalent Canadian reference laboratory)

Concomitant aerosolized antibiotic treatment: subjects receiving intermittent (alternating month on/month off) aerosolized antibiotic treatment are eligible, but must be at least 1 week into their off-treatment cycle at the time of baseline assessment.

Subjects receiving continuous aerosolized antibiotic treatment will be eligible without restriction on their aerosolized antibiotic treatment

Chest radiograph, computed tomography (CT) or magnetic resonance imaging (MRI), (most recent, obtained within 90 days of screening) without significant acute findings (e.g., infiltrates [lobar or diffuse interstitial], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (e.g., chronic scarring or atelectasis) are allowed

Subjects (and parent/guardian as required) must be able to provide written informed consent/assent prior to any study related procedures

Ability to perform reproducible pulmonary function tests

Sexually active females of childbearing potential must agree to use a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of study drug. A highly effective method of birth control is defined as a method that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), or a vasectomized partner

Exclusion Criteria:
Administration of any investigational drug or use of any investigational device within 28 days of randomization/baseline and within six half-lives of the investigational drug (whichever is longer)
Administration of AZLI treatment within the 28 days prior to randomization/baseline

Known local or systemic hypersensitivity to monobactam antibiotics

History of lung transplantation

Abnormal renal or hepatic function results at most recent test within the previous 90 days, defined as:
AST or ALT > 5 times upper limit of normal (ULN) range
Serum creatinine > 2 times ULN

Known portal hypertension or complications of CF hepatopathy

Positive urine pregnancy test (confirmed by serum pregnancy test) at screening; all women of childbearing potential will be tested

Female of childbearing potential who is lactating or not practicing a highly effective method of birth control as defined in Section 7.8

Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01059565
Contacts
Contact: Sheila Leitzinger
2062564904
sheila.leitzinger@gilead.com
Contact: Jennifer Glover
2067923039
jennifer.glover@gilead.com Hide Study Locations

Locations

United States, Alabama
Pulmonary Associates of Mobile, P.C.
Mobile, Alabama, United States, 36608

United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016

United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205

United States, California
University of Southern California
Los Angeles, California, United States, 90033

United States, Colorado
National Jewish Health
Denver, Colorado, United States, 80206

United States, Connecticut
Hartford Hospital
Hartford, Connecticut, United States, 06102

United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803

United States, Florida
Tampa General Hospital
Tampa, Florida, United States, 33606

University of Miami
Miami, Florida, United States, 33136
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207

United States, Illinois
The Cystic Fibrosis Institute
Glenview, Illinois, United States, 60025

United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
UMass Medical Center
Worcester, Massachusetts, United States, 01605

United States, Michigan
Harper University Hospital/Wayne State University
Detroit, Michigan, United States, 48201
University of Michigan
Ann Arbor, Michigan, United States, 48109

United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455

United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216

United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110

United States, Nevada
Childrens Lung Specialists
Las Vegas, Nevada, United States, 89107

United States, New Jersey
Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903

Morristown Memorial Hospital
Morristown, New Jersey, United States, 07962

United States, New Mexico
Univesity of New Mexico
Albuquerque, New Mexico, United States, 87131

United States, New York
The Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040

United States, North Carolina
UNC Chapel Hill
Chapel Hill, North Carolina, United States, 27599

United States, Ohio
Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308
Toledo Children's Hospital/The Toledo Hospital
Toledo, Ohio, United States, 43606

United States, Oklahoma
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, United States, 73112

United States, Oregon
Oregon Health and Sciences University
Portland, Oregon, United States, 97239

Kaiser Permanente Northwest
Portland, Oregon, United States, 97227

United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15201
Penn State Inst & Milton S. Hershey Med Ctr
Hershey, Pennsylvania, United States, 17033
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina
MUSC
Charleston, South Carolina, United States, 29425

University of South Carolinas School of Medicine
Columbia, South Carolina, United States, 29203

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298

Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507

United States, West Virginia
Pediatric Infectious Diseases
Morgantown, West Virginia, United States, 26506

United States, Wisconsin
Medical College of Wisconsin, Children's Hospital Wisconsin
Milwaukee, Wisconsin, United States, 53201

Canada, Ontario
St Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8