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

Pulmonary Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01519661
• Other study ID #: CTBM100C2401
• Secondary ID: 2011-002000-32
• Status: Completed
• Phase: Phase 4
• First received: January 24, 2012
• Last updated: February 8, 2015
• Start date: January 2012
• Est. completion date: January 2014

Study information

• Verified date: February 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis
• Pseudomonas Aeruginosa in Cystic Fibrosis
• Pulmonary Infections

Intervention

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.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Argentina	Novartis Investigative Site	Córdoba	Cordoba
Argentina	Novartis Investigative Site	Paraná	Entre Rios
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	New Lambton Heights	New South Wales
Australia	Novartis Investigative Site	Parkville	Victoria
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Montreal	Quebec
France	Novartis Investigative Site	Giens Cedex
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Roscoff
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Hungary	Novartis Investigative Site	Budapest
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Palermo
Italy	Novartis Investigative Site	Roma
Italy	Novartis Investigative Site	Verona	VR
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Monterrey	Nuevo León
Spain	Novartis Investigative Site	Barcelona	Cataluña
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Morristown	New Jersey
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  France,  Germany,  Hungary,  Italy,  Mexico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths	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.	337 days	Yes
Secondary	Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted	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.	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.	No
Secondary	Relative Change From Baseline in FVC Percent Predicted	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.	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.	No
Secondary	Relative Change From Baseline in FEF Rate Over 25 to 75 Percent of Vital Capacity Predicted	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.	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.	No
Secondary	Change From Baseline in Pseudomonas Aeruginosa Colony Forming Units in Sputum	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.	Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337	No
Secondary	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	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.	Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337	Yes
Secondary	Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events		Day 337	Yes
Secondary	Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events	The total number of hospitalization days due to serious respiratory-related adverse events was analyzed.	Day 337	No
Secondary	Time to First Hospitalization Due to Serious Respiratory-related Adverse Events	The day of first hospitalization due to serious respiratory-related adverse events was analyzed.	Day 337	No
Secondary	Percentage of Participants Who Used New Anti-pseudomonal Antibiotics		Day 337	No
Secondary	Number of Days of New Anti-pseudomonal Antibiotic Use	The total number of days of new anti-pseudomonal antibiotic use was analyzed.	Day 337	No
Secondary	Time to Use of New Anti-pseudomonal Antibiotic	Time to first use of new anti-pseudomonal antibiotic was analyzed.	Day 337	No