Assess the 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: May 22, 2014
Last verified: May 2014
  Purpose

This study will assess 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:
  • Incidence of treatment emergent adverse events [ Time Frame: 337days ] [ Designated as safety issue: Yes ]
    Adverse events will be deemed treatment-emergent if the onset date/time is on or after the date and time of first study drug. All adverse events will be included after this time, this included during both on and off-treatment periods.


Secondary Outcome Measures:
  • Relative change in forced expiratory volume in one second percent predicted [ Time Frame: Day 57, day 113, day 169, day 225, day 281, day 337 ] [ Designated as safety issue: No ]
    This assessment will be measured by pulmonary function testing using spirometry. During each visit, pulmonary function testing will be measured by at least three acceptable forced expiratory maneuvers, which have to comply with ATS/ERS criteria.

  • Relative change in forced expiratory flow rate over 25 to 75 percent of vital capacity predicted [ Time Frame: Day 57, day 113, day 169, day 225, day 281, day 337 ] [ Designated as safety issue: No ]
    This assessment will be measured by pulmonary function testing using spirometry. During each visit, pulmonary function testing will be measured by at least three acceptable forced expiratory maneuvers, which have to comply with ATS/ERS criteria

  • Relative change in Pseudomonas aeruginosa colony forming units in sputum [ Time Frame: Day 1-day 29, Day 1 - 85, Day 1 - 141, Day 1-197, Day1-253, Day1-309 ] [ Designated as safety issue: No ]
    Sputum will be collected in sterile containers and cultured for Cystic Fibrosis respiratory pathogens

  • Change in Pseudomonas aeruginosa tobramycin minimal inhibitory concentration [ Time Frame: Day 1-day 29, Day 1 - 85, Day 1 - 141, Day 1-197, Day1-253, Day1-309, day 337 ] [ Designated as safety issue: No ]
    Sputum will be collected in sterile containers and cultured for Cystic Fibrosis respiratory pathogens. Minimal inhibitory concentration values for Pseudomonas aeruginosa will assess change in pathogen susceptibility to tobramycin. Aztreonam, ceftazidime, meropenem, imipenem and ciprofloxacin minimal inhibitory concentration values will also be determined.

  • Rate of hospitalization due to serious respiratory-related adverse events and time to first hospitalization due to serious respiratory-related adverse events [ Time Frame: Day 1-day 29, Day 1 - 85, Day 1 - 141, Day 1-197, Day1-253, Day1-309, day 337 ] [ Designated as safety issue: No ]
    A count of hospitalization and day of first hospitalization will be analyzed.

  • Rate of use of anti-pseudomonal antibiotic and time to the use of anti-pseudomonal antibiotic [ Time Frame: Day 1 - 337 ] [ Designated as safety issue: No ]
    Both a count and the day of first use of anti-pseudomonal antibiotic will be analyzed.

  • To evaluate the safety profile of TIP in terms of clinical laboratory results and, (in a subset of patients) audiology throughout the treatment period. [ Time Frame: Day 1 - 337 ] [ Designated as safety issue: Yes ]
    For laboratory, summaries on Mean laboratory results and abnormal results. For audiology, decreases in consecutive hearing frequencies


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: TIP
Eligible patients will be 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 consists of 112mg tobramycin (4 capsules of 28mg each), the total daily dose corresponds to 224mg tobramycin (112mg b.i.d.). These 56 days represent 1 cycle of therapy.
Drug: TBM100
Tobramycin inhalation powder will be assigned to four capsules at 28mg dosage strength. It will be 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 anti-pseudomonal antibiotic are not allowed
  • Use of loop diuretics within 7 days prior to study drug administration

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
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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
Last Updated: May 22, 2014
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:
Fibrosis
Cystic Fibrosis
Respiratory Aspiration
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Respiration Disorders
Tobramycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014