Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles

A 24-week, Open-label, Parallel-group, Interventional Phase IV Study Comparing Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles for the Treatment of Pulmonary Pseudomonas Aeruginosa in Patients With Cystic Fibrosis

To provide efficacy and safety data comparing two dosing schedules of Tobramycin Inhalation Powder (TIP) for the treatment of pulmonary Pseudomonas aeruginosa in patients with cystic fibrosis.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Tobramycin Inhalation Powder

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608-1128
      • Novartis Investigative Site
  • California
    • Los Angeles, California, United States, 90027
      • Novartis Investigative Site
    • Sacramento, California, United States, 95819
      • Novartis Investigative Site
    • Ventura, California, United States, 93003
      • Novartis Investigative Site
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Novartis Investigative Site
    • Jacksonville, Florida, United States, 32207
      • Novartis Investigative Site
    • Miami, Florida, United States, 33136
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32504
      • Novartis Investigative Site
  • Illinois
    • Glenview, Illinois, United States, 60025
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Novartis Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novartis Investigative Site
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Novartis Investigative Site
  • New York
    • New Hyde Park, New York, United States, 11040
      • Novartis Investigative Site
    • New York, New York, United States, 10595
      • Novartis Investigative Site
  • Ohio
    • Akron, Ohio, United States, 44308
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 92772
      • Novartis Investigative Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-8050
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78723
      • Novartis Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • 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

Description

Inclusion Criteria:

1. Provide written informed consent, HIPPA (Health Insurance Portability and Accountability Act) authorization (where applicable), and assent (as appropriate) prior to the performance of any study-related procedure.
2. Confirmed diagnosis of CF
3. FEV1 at screening (Visit 1) ≥25% and ≤ 80% of normal predicted values for age, sex, and height
4. P. aeruginosa must be present within 6 months prior to screening and at screening
5. Able to comply with all protocol requirements
6. Clinically stable in the opinion of the investigator

Exclusion Criteria:

1. History of Burkholderia cenocepacia (Bcc) complex within 2 years prior to screening and/or Bcc complex at screening
2. Hemoptysis more than 60 cc at any time within 30 days prior to study drug administration
3. History of hearing loss or chronic tinnitus deemed clinically significant by the investigator
4. Serum creatinine 2 mg/dL or greater, BUN 40 mg/dL or greater, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening
5. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics
6. Patients who are unable to discontinue previously received inhaled antibiotic regimen(s) (inhaled antibiotics are not allowed other than study drug)
7. Use of inhaled aminoglycosides within 28 days prior to study drug administration (Visit 2)
8. Use of systemic anti-pseudomonal antibiotics within 28 days prior to study drug administration
9. Use of loop diuretics within 7 days prior to study drug administration
10. Administration of any investigational drug within 30 days prior to enrollment or 5 half-lives, whichever is longer
11. Signs and symptoms of acute pulmonary disease, e.g , pneumonia, pneumothorax
12. Hospitalization during the baseline visit
13. History of malignancy
14. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening
15. Patients with other clinically significant conditions (not associated with the study indication) which might interfere with the assessment of this study
16. Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable
17. Pregnant or nursing (lactating) women
18. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Tobramycin Inhalation Powder (112 mg) once daily during 168 days	Drug: Tobramycin Inhalation Powder; Tobramycin Inhalation Powder 112 mg (four 28-mg capsules) taken via inhaler once or twice a day, depending on study arm
Active Comparator: Arm 2; Tobramycin Inhalation Powder (112 mg) twice daily on days 1-28, days 57-84 and days 113-140	Drug: Tobramycin Inhalation Powder; Tobramycin Inhalation Powder 112 mg (four 28-mg capsules) taken via inhaler once or twice a day, depending on study arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Forced Expiratory Volume in 1 Second ( FEV1) Percent Predicted	The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function.	Baseline and Day 168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Percent Predicted	The Forced Expiratory Volume in 1 second (FEV1) percent predicted expresses FEV1 as a percentage of the "predicted values" for participants of similar characteristics (height, age, sex, and sometimes race and weight). A positive change from baseline in FEV1 percent predicted indicates improvement in lung function.	Baseline and Day 168
Percent Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted	Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC will be assessed via spirometry. A positive change from baseline in FVC indicates improvement in lung function.	Baseline and Day 168
Percent Change From Baseline in Forced Expiratory Flow (FEF) 25%-75% Predicted	The Forced Expiratory Flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. A positive change from baseline in FEF indicates improvement in lung function. The predicted percent will be assessed.	Baseline and day 168
Change From Baseline in Pseudomonas Aeruginosa Sputum Density	Change from baseline in Pseudomonas aeruginosa sputum density will be measured by log10 colony forming units per gram of sputum.	Baseline and day 168
Time to First Hospitalization Due to Respiratory-related Events	Time to the first hospitalization due to respiratory-related events (number of days) per patient.	Day 1 to day 168
Percentage of Patients With Hospitalizations Due to Respiratory-related Events	Percentage of patients with hospitalization due to respiratory-related events	Day 1 to day 168
Length of Hospital Stay Due to Respiratory-related Events	The number of days in length of hospital stay per patient due to respiratory-related events will be measured.	Day 1 to day 168
Time to First Usage of Anti-pseudomonal Antibiotic	Time to first usage of anti-pseudomonal antibiotic per patient will be assessed by number of days	Day 1 to day 168
Percentage of Patients Who Use Anti-pseudomonal Antibiotic	Percentage of patients who use anti-pseudomonal antibiotic will be assessed.	Day 1 to day 168
Duration of Use of Anti-pseudomonal Antibiotic	Number of days of use of anti-pseudomonal antibiotic per patient will be assessed.	Day 1 to day 168
Change From Baseline in Tobramycin Minimal Inhibitory Concentration for Pseudomonas Aeruginosa	Change from baseline in tobramycin minimal inhibitory concentration for Pseudomonas aeruginosa will be measured by laboratory testing.	Baseline and day 168

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: December 13, 2013
• First Submitted That Met QC Criteria: December 18, 2013
• First Posted (Estimate): December 19, 2013

Study Record Updates

• Last Update Posted (Actual): March 29, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; CF
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Anti-Infective Agents; Anti-Bacterial Agents; Tobramycin
• Other Study ID Numbers: CTBM100CUS03