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

Phase 4

Completed

Conditions: Pulmonary Infections
Pseudomonas Aeruginosa in Cystic Fibrosis

Interventions: Drug: TBM100

Registration Number: NCT01519661

Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 157

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

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tobramycin Inhalation Powder (TIP)	TBM100	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment Emergent Adverse Events, Serious Adverse Events (SAEs) and Deaths	337 days	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

Name	Time	Method
Relative Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Percent Predicted	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.	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	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.	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	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.	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	Baseline, day 1, day 29, day 85, day 141, day 197, day 253, day 309, day 337	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.
Number of Hospitalization Days Due to Serious Respiratory-related Adverse Events	Day 337	The total number of hospitalization days due to serious respiratory-related adverse events was analyzed.
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	Baseline, day 29, day 85, day 141, day 197, day 253, day 309, day 337	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.
Number of Days of New Anti-pseudomonal Antibiotic Use	Day 337	The total number of days of new anti-pseudomonal antibiotic use was analyzed.
Percentage of Participants Hospitalized Due to Serious Respiratory-related Adverse Events	Day 337
Time to First Hospitalization Due to Serious Respiratory-related Adverse Events	Day 337	The day of first hospitalization due to serious respiratory-related adverse events was analyzed.
Percentage of Participants Who Used New Anti-pseudomonal Antibiotics	Day 337
Time to Use of New Anti-pseudomonal Antibiotic	Day 337	Time to first use of new anti-pseudomonal antibiotic was analyzed.