Observational Study in Cystic Fibrosis Patients Using TOBI® PODHALER® or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs

A Prospective Observational Study in Cystic Fibrosis Patients With Chronic Respiratory Pseudomonas Aeruginosa Infection Treated With TOBI® PODHALER® (Tobramycin Inhalation Powder) or Other FDA Approved Inhaled Antipseudomonal Antibacterial Drugs

This is a multicenter, prospective, two cohort, observational study over a 5-year period in Cystic Fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection.The study will collect data over 1 year on respiratory function, antibacterial effectiveness, and clinical outcomes of treatment with inhaled antipseudomonal antibiotics and data over 5 years on microbiological and safety assessments.

Study Overview

• Status: Completed
• Conditions: Pseudomonas Aeruginosa in Cystic Fibrosis
• Intervention / Treatment: Drug: TOBI® PODHALER®; Drug: TOBI®; Drug: Bethkis®; Drug: Cayston®

Detailed Description

This study will include CF patients chronically colonized with P. aeruginosa enrolled in the Cystic Fibrosis Foundation (CFF) PortCF registry and using TOBI® PODHALER® or another FDA-approved inhaled antipseudomonal antibiotic. No therapeutic intervention will be assigned and physicians will use their discretion in choosing a treatment regimen for their patients.

Sputum samples (primarily collected during routine clinical follow-up) from patients able to spontaneously produce sputum will be sent to a central laboratory for analysis.

In addition, this study will include two optional sub-studies for qualifying patients in the first study year - Sputum microbiology sub-study and TOBI® PODHALER® sputum pharmacokinetics (PK) sub-study.

• Study Type: Observational
• Enrollment (Actual): 409

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Novartis Investigative Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Novartis Investigative Site
  • California
    • Bellflower, California, United States, 90706
      • Novartis Investigative Site
    • Fullerton, California, United States, 92831
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90027
      • Novartis Investigative Site
    • Madera, California, United States, 93636
      • Novartis Investigative Site
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Novartis Investigative Site
    • New Haven, Connecticut, United States, 06519
      • Novartis Investigative Site
    • Stamford, Connecticut, United States, 06902
      • Novartis Investigative Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Novartis Investigative Site
    • Miami, Florida, United States, 33136
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32803
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33606
      • Novartis Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Novartis Investigative Site
  • Idaho
    • Boise, Idaho, United States, 83712
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5225
      • Novartis Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novartis Investigative Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 97205
      • Novartis Investigative Site
    • Grand Rapids, Michigan, United States, 49503
      • Novartis Investigative Site
    • Ypsilanti, Michigan, United States, 48197
      • Novartis Investigative Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Novartis Investigative Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Novartis Investigative Site
  • Montana
    • Billings, Montana, United States, 59101
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Novartis Investigative Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Novartis Investigative Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 8901
      • Novartis Investigative Site
  • New York
    • New Hyde Park, New York, United States, 11040
      • Novartis Investigative Site
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Novartis Investigative Site
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-085
      • Novartis Investigative Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Novartis Investigative Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Novartis Investigative Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Novartis Investigative Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78723
      • Novartis Investigative Site
    • Dallas, Texas, United States, 75390
      • Novartis Investigative Site
    • Tyler, Texas, United States, 75708
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Novartis Investigative Site
  • Vermont
    • Burlington, Vermont, United States, 5405
      • Novartis Investigative Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Novartis Investigative Site
    • Richmond, Virginia, United States, 23298
      • Novartis Investigative Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

CF patients chronically colonized with P. aeruginosa enrolled in the Cystic Fibrosis Foundation (CFF) PortCF registry and using TOBI® PODHALER® (TOBI® PODHALER®-treated cohort) or another FDA-approved inhaled antipseudomonal antibiotic (non-TOBI® PODHALER®-treated cohort).

It is anticipated that this patient population will include a subset of patients with increased P. aeruginosa MICs to tobramycin at baseline.

Description

Inclusion Criteria:

• ≥ 6 years of age.
• Documented FEV1 ≥ 25% predicted in the previous year.
• Diagnosis of cystic fibrosis.
• Established diagnosis of chronic P. aeruginosa infection of the lungs defined as two or more positive P. aeruginosa cultures in the previous year as documented in the subject's medical history (this may include a history of one positive culture in the year prior to enrollment and one positive culture from the specimen collected at the baseline visit).
• Prescribed and initiated chronic treatment with FDA-approved inhaled antipseudomonal antibiotic for chronic P. aeruginosa infection (e.g. TOBI® PODHALER®, TOBI®, Cayston® and Bethkis®).
• Actively enrolled or willingness to enroll in PortCF registry.
• Willing and able to provide written informed consent or, parent/guardian consent and where applicable pediatric assent, for participation and use of relevant clinical data previously captured in PortCF.
• Anticipated to have good adherence to routine visits, defined as the investigator having good knowledge that the patient has been to at least 2-3 routine visits in the previous year.

Exclusion Criteria:

• Documented FEV1 < 25% predicted in the previous year.
• Current participation in an interventional clinical study with an inhaled antibiotic treatment.
• Treatment with compounded tobramycin (e.g. the use of tobramycin IV solution adapted for use by inhalation).
• Treatment with inhaled antipseudomonal antibacterial drug(s) that are not FDA approved.
• Patients undergoing an early eradication regimen for CF (first line therapy).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TOBI® PODHALER® cohort	Drug: TOBI® PODHALER®
non-TOBI® PODHALER® cohort; Approximately 250 patients treated with other FDA-approved inhaled antipseudomonal antibacterial drugs at enrollment	Drug: TOBI®; tobramycin inhalation solution, USP; Drug: Bethkis®; tobramycin inhalation solution; Drug: Cayston®; aztreonam for inhalation solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute change in forced expiratory volume in one second (FEV1) percent predicted from baseline.	1 year
Absolute change from baseline in the number of P. aeruginosa colony forming units in sputum.	1 year
Minimum inhibitory concentration (MIC) of tobramycin and the following antipseudomonal antibacterial drugs (meropenem, imipenem, ceftazidime, aztreonam and ciprofloxacin) for P. aeruginosa sputum isolates in both treatment cohorts.	Up to 5 years
Frequency of the following treatment emergent pathogens in sputum: S. aureus (MRSA and MSSA), S. maltophilia, A. xylosoxidans, and Burkholderia spp.in both treatment cohorts.	Up to 5 years
Number of pulmonary exacerbations and those leading to hospitalization.	1 year
Proportion of patients experiencing pulmonary exacerbations including those leading to hospitalization.	1 year
Incidence rate of patients with one or more pulmonary exacerbations.	1 year
Incidence rate of pulmonary exacerbations.	1 year
Time to first pulmonary exacerbation.	1 year
Use of additional antipseudomonal antibiotics (overall, IV, oral) to treat pulmonary exacerbations.	1 year
Mortality rate	1 year
Pharmacokinetic properties of TOBI® PODHALER® as measured by sputum specimens collected during the on-treatment cycles.	1 year
Number of respiratory related hospitalizations.	1 year
Duration of stay for respiratory related hospitalizations.	1 year
Number of non-respiratory related hospitalizations.	1 year
Duration of stay for non-respiratory related hospitalizations.	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Relative change in FEV1 % predicted from baseline.	1 year

Collaborators and Investigators

• Sponsor: Mylan Inc.
• Collaborators: Cystic Fibrosis Foundation

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2015
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 15, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Pseudomonas Infections; Anti-Infective Agents; Anti-Bacterial Agents; Tobramycin
• Other Study ID Numbers: CTBM100C2407