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

NCT01059565 | Completed Phase 3 Results DMC

• 1 other identifier: GS-US-205-0127
• Study Type: interventional
• Target: 102
• Locations: 2 countries
• Sites: 35

Brief Summary

The purpose of this research study was to determine if an experimental drug called Aztreonam for Inhalation Solution (AZLI) was safe and effective to treat Burkholderia lung infections in patients with cystic fibrosis (CF). Spirometry was used to assess pulmonary function, and the revised Cystic Fibrosis Questionnaire (CFQ-R) was used to assess quality of life. The CFQ-R is a validated, patient-reported outcome tool used to measure health-related quality of life for children and adults with CF. The study consisted of a 24-week randomized phase, and a 24-week open-label phase. Primary and secondary efficacy analyses were conducted for the 24-week randomized phase only. Safety data were collected for both the randomized and open-label phases.

Conditions

Cystic Fibrosis; Burkholderia Infections

Keywords

Cystic Fibrosis; Aztreonam Lysine; lung infection; Burkholderia; CFQ-R; inhaled antibiotic

Outcome Measures

Primary Outcomes (1)

• AUCave of Relative Change in FEV1 % Predicted From Baseline to Week 24

  The relative change (AUCave) in FEV1 % predicted from baseline to Week 24 was analyzed. FEV1 % predicted is defined as FEV1 % of the patient divided by the average FEV1 % in the population for any person of similar age, sex and body composition. AUCave is the calculated area under the curve corrected for baseline and adjusted by the number of days on study through Week 24.

  Baseline to Week 24

Secondary Outcomes (13)

• Total Number of Systemic and/or Inhaled Antibiotic Courses for Respiratory Events

  Baseline to Week 24

• AUCave of Change in CFQ-R RSS Scores From Baseline to Week 24

  Baseline to Week 24

• AUCave of Relative Change From Baseline to Week 24 in FEV1

  Baseline to Week 24

• AUCave of Relative Change From Baseline to Week 24 in FVC

  Baseline to Week 24

• AUCave of Relative Change From Baseline to Week 24 in FEF25-75

  Baseline to Week 24

Study Arms (2)

AZLI

EXPERIMENTAL

Participants were randomized to receive AZLI for up to 24 weeks and may have continued to receive AZLI during the open-label phase for up to an additional 24 weeks.

Drug: AZLI

Placebo

PLACEBO COMPARATOR

Participants were randomized to receive placebo to match AZLI for up to 24 weeks and may have switched to AZLI during the open-label phase for up to 24 weeks.

Drug: Placebo

Interventions

AZLI DRUG

Aztreonam for inhalation solution (AZLI; 75 mg aztreonam/52.5 mg lysine monohydrate) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer.

AZLI

Placebo DRUG

Placebo to match AZLI (lactose and sodium chloride) was administered three times a day, with at least 4 hours between doses, using the investigational nebulizer.

Placebo

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:

• Male or female ≥ 6 years of age
• Subjects with CF as diagnosed by one of the following:
• Documented sweat chloride ≥ 60 milliequivalent (mEq)/L by quantitative pilocarpine iontophoresis test
• Documented sweat sodium ≥ 60 mmol/L
• Two well-characterized genetic mutations in the CF transmembrane conductance regulator (CFTR) gene
• Abnormal nasal potential difference (NPD) with accompanying symptoms characteristic of CF
• Chronic infection with Burkholderia spp. defined by:
• One sputum (or bronchoalveolar lavage) culture positive for Burkholderia spp. within 6 months prior to baseline assessment,
• At least 50% of sputum (or bronchoalveolar lavage) 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 (or bronchoalveolar lavage) culture (obtained at any point in time) confirmed to be Burkholderia spp. by the Cystic Fibrosis Foundation (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 were eligible, but must have been at least 1 week into their off-treatment cycle at the time of baseline assessment. Subjects receiving continuous aerosolized antibiotic treatment were 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 (eg, infiltrates \[lobar or diffuse interstitial\], pleural effusion, pneumothorax), and no significant intercurrent illness; chronic, stable findings (eg, chronic scarring or atelectasis) were allowed.
• Subjects (and parent/guardian as required) must have been 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 have agreed 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 was defined as a method that would result in a low failure rate (ie, 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.

You may not qualify if:

• 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:
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times the upper limit of the normal range (ULN)
• 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 were tested
• Any female of childbearing potential who was lactating or not practicing a highly effective method of birth control as defined in the protocol
• Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would have interfered with subject treatment, assessment or compliance with the protocol

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (35)

Unknown Facility

Mobile, Alabama, 36608, United States

Location

Unknown Facility

Phoenix, Arizona, 85016, United States

Location

Unknown Facility

Little Rock, Arkansas, 72205, United States

Location

Unknown Facility

Denver, Colorado, 80206, United States

Location

Unknown Facility

Hartford, Connecticut, 06102, United States

Location

Unknown Facility

Wilmington, Delaware, 19803, United States

Location

Unknown Facility

Jacksonville, Florida, 32207, United States

Location

Unknown Facility

Miami, Florida, 33136, United States

Location

Unknown Facility

Tampa, Florida, 33606, United States

Location

Unknown Facility

Glenview, Illinois, 60025, United States

Location

Unknown Facility

Boston, Massachusetts, 02115, United States

Location

Unknown Facility

Worcester, Massachusetts, 01605, United States

Location

Unknown Facility

Detroit, Michigan, 48201, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55455, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

Las Vegas, Nevada, 89107, United States

Location

Unknown Facility

Morristown, New Jersey, 07962, United States

Location

Unknown Facility

New Brunswick, New Jersey, 08903, United States

Location

Unknown Facility

Albuquerque, New Mexico, 87131, United States

Location

Unknown Facility

New Hyde Park, New York, 11040, United States

Location

Unknown Facility

Chapel Hill, North Carolina, 27599, United States

Location

Unknown Facility

Akron, Ohio, 44308, United States

Location

Unknown Facility

Columbus, Ohio, 43205, United States

Location

Unknown Facility

Toledo, Ohio, 43606, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73112, United States

Location

Unknown Facility

Portland, Oregon, 97239, United States

Location

Unknown Facility

Hershey, Pennsylvania, 17033, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, 15201, United States

Location

Unknown Facility

Charleston, South Carolina, 29425, United States

Location

Unknown Facility

Columbia, South Carolina, 29203, United States

Location

Unknown Facility

Richmond, Virginia, 23298, United States

Location

Unknown Facility

Morgantown, West Virginia, 26506, United States

Location

Unknown Facility

Milwaukee, Wisconsin, 53201, United States

Location

Unknown Facility

Toronto, Ontario, M5B 1W8, Canada

Location

MeSH Terms

Conditions

Cystic Fibrosis; Burkholderia Infections

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

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 1, 2010
• Study Start: February 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: January 1, 2012
• Last Updated: March 11, 2014
• Results First Posted: March 11, 2014

Record last verified: 2014-02

Locations

US (34); CA (1)