Long Term Safety of Tobramycin Inhalation Powder in Patients With Cystic Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01519661
First received: January 24, 2012
Last updated: February 8, 2015
Last verified: February 2015
  Purpose

This study assessed the long term safety data for the use of tobramycin inhalation powder in patients suffering from cystic fibrosis who have a chronic pulmonary infection with Pseudomonas aeruginosa.


Condition Intervention Phase
Pulmonary Infections
Pseudomonas Aeruginosa in Cystic Fibrosis
Drug: TBM100
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm, Open-label, Multicenter, Phase IV Trial to Assess Long Term Safety of Tobramycin Inhalation Powder (TIP) in Patients With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths [ Time Frame: 337 days ] [ Designated as safety issue: Yes ]
    Adverse events were deemed treatment-emergent if the onset date/time was on or after the date and time of first study drug. All adverse events were included after this time during both on and off-treatment periods.


Secondary Outcome Measures:
  • Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted [ Time Frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. ] [ Designated as safety issue: No ]
    Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEV1 % predicted from baseline to pre-dose day X = ((pre-dose day X FEV1 % predicted - baseline FEV1 % predicted) / baseline FEV1 % predicted) • 100.

  • Relative Change From Baseline in FVC Percent Predicted [ Time Frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. ] [ Designated as safety issue: No ]
    Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recorded at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FVC % predicted from baseline to pre-dose day X = ((pre-dose day X FVC % predicted - baseline FVC % predicted) / baseline FVC % predicted) • 100.

  • Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted [ Time Frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337. All study visits except baseline and day 337 occurred at the end of a 28-day on-treatment period of a cycle. Day 337 was the end of the final 28-day off treatment period. ] [ Designated as safety issue: No ]
    Spirometry was performed at each visit. FEV1, FVC, and FEF25-75 were recored at all visits according to American Thoracic Society (ATS) guidelines. FEV1 = the volume of air expired in 1 second. FEV1 % predicted is a normalized value of FEV1 calculated using the Knudsen equation, based upon participant's age, gender and height. FVC (forced vital capacity) = the maximal volume of air exhaled with maximally forced effort from a position of maximal inspiration. FEF25-75 = forced expiratory flow from 25% to 75% of the FVC. Relative change in FEEF25-75 from baseline to pre-dose day X = ((pre-dose day X FEF25-75 - baseline FEF25-75) / baseline FEF25-75) • 100.

  • Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum [ Time Frame: Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337 ] [ Designated as safety issue: No ]
    Sputum was collected in sterile containers and cultured for Pseudomonas aeruginosa (Pa.) (quantitative test) and other typical Cystic Fibrosis respiratory pathogens. The Pa. biotypes measured were mucoid, dry and small colony variant. Results are presented for the sum of all biotypes of Pa, with data transformed using a base 10 logarithm.

  • Tobramycin MIC 50 and MIC 90 Values Over All Isolates for the Sum of All Biotypes (Mucoid, Dry and Small Colony Variant) of Pseudomonas Aeruginosa [ Time Frame: Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337 ] [ Designated as safety issue: Yes ]
    Tobramycin MIC 50 and MIC 90 values were defined as the lowest concentration of tobramycin required to inhibit 50% and 90%, respectively, of the P. aeruginosa strains tested.

  • Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events [ Time Frame: Day 337 ] [ Designated as safety issue: Yes ]
  • Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events [ Time Frame: Day 337 ] [ Designated as safety issue: No ]
    The total number of hospitalization days due to serious respiratory-related adverse events was analyzed.

  • Time to First Hospitalization Due to Serious Respiratory-related Adverse Events [ Time Frame: Day 337 ] [ Designated as safety issue: No ]
    The day of first hospitalization due to serious respiratory-related adverse events was analyzed.

  • Percentage of Participants Who Used New Anti-pseudomonal Antibiotics [ Time Frame: Day 337 ] [ Designated as safety issue: No ]
  • Number of Days of New Anti-pseudomonal Antibiotic Use [ Time Frame: Day 337 ] [ Designated as safety issue: No ]
    The total number of days of new anti-pseudomonal antibiotic use was analyzed.

  • Time to Use of New Anti-pseudomonal Antibiotic [ Time Frame: Day 337 ] [ Designated as safety issue: No ]
    Time to first use of new anti-pseudomonal antibiotic was analyzed.


Enrollment: 157
Study Start Date: January 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tobramycin Inhalation Powder (TIP)
Eligible patients were assigned to four capsules of TIP at 28mg dosage strength, inhaled b.i.d. in the morning and in the evening via the T-326 inhaler, for 28 days (on treatment), followed by 28 days of no study treatment (off treatment). Each treatment therefore consisted of 112mg tobramycin (4 capsules of 28mg each) with the total daily dose = 224mg tobramycin (112mg b.i.d.). These 56 days represented 1 cycle of therapy.
Drug: TBM100
Tobramycin inhalation powder was assigned as four capsules at 28mg dosage strength. It was inhaled b.i.d in the morning and in the evening via the T-326 Inhaler.

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of Cystic Fibrosis
  • FEV1 at screening must be between 25 and 75 percent of normal predicted values for age, sex and height based on the Knudson equation
  • Pseudomonas aeruginosa must be present in a sputum / deep cough throat swab culture or bronchoalveolar lavage within 6 months prior to screening and in the sputum/deep-throat cough swab culture at screening

Exclusion Criteria:

  • History of sputum culture or deep cough throat swab culture yielding Burkholderia cenocepacia complex within 2 years prior to screening and /or sputum culture yielding Burkholderia cenocepacia at screening
  • Hemoptysis more than 60mL at any time within 30 days prior to study drug administration
  • History of hearing loss or chronic tinnitus deemed clinically significant
  • Serum creatinine 2mg/dl or more, BUN 40mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening
  • Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics
  • Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic
  • Any use of inhaled or systemic anti-pseudomonal antibiotic within 28 days prior to study drug administration
  • Use of loop diuretics within 7 days prior to study drug administration

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519661

  Show 49 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01519661     History of Changes
Other Study ID Numbers: CTBM100C2401, 2011-002000-32
Study First Received: January 24, 2012
Results First Received: December 17, 2014
Last Updated: February 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Tobramycin Inhalation powder
Cystic fibrosis
Lung disease
Anti-bacterial agents

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2015