A 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

• Register: EUCTR
• Last refreshed on: 22 May 2017
• Main ID: EUCTR2016-004318-82-Outside-EU/EEA
• Date of registration: 15/05/2017
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals Corporation
• Public title: A 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
• Scientific title: Tobramycin Inhalation Powder (TIP) Administered Once Daily Continuously Versus TIP Administered BID in 28 Day on / 28 Day Off Cycles
• Target sample size: 200
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004318-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: TOBI Podhaler cyclical use Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma AG

Key inclusion & exclusion criteria

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.
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

Are the trial subjects under 18? yes
Number of subjects for this age range: 3
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: LLT Classification code 10021860 Term: Infection Pseudomonas aeruginosa System Organ Class: 100000004862

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: TOBI Podhaler
Pharmaceutical Form: Capsule
INN or Proposed INN: Tobramycin
Other descriptive name: TOBRAMYCIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 112-

Primary Outcome(s)

Primary end point(s): Change from baseline in Forced Expiratory Volume in 1 second ( FEV1) percent predicted [ Time Frame: Baseline and Day 168 ]
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.

Main Objective: 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.

Timepoint(s) of evaluation of this end point: Time Frame: Baseline and Day 168

Secondary Objective: 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.

Secondary Outcome(s)

Secondary end point(s): Percent change from baseline in Forced Expiratory Volume in 1 second (FEV1) percent predicted [ Time Frame: Baseline and Day 168 ]
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.

•Percent change from baseline in Forced Vital Capacity (FVC) percent predicted [ Time Frame: Baseline and Day 168 ]
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.

•Percent change from baseline in forced expiratory flow (FEF) 25%-75% predicted [ Time Frame: Baseline and day 168 ]
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.

•Change from baseline in Pseudomonas aeruginosa sputum density [ Time Frame: Baseline and day 168 ]
Change from baseline in Pseudomonas aeruginosa sputum density will be measured by log10 colony forming units per gram of sputum.

•Time to first hospitalization due to respiratory-related events [ Time Frame: Day 1 to day 168 ]
Time to the first hospitalization due to respiratory-related events (number of days) per patient.

•Percentage of patients with hospitalizations due to respiratory-related events [ Time Frame: Day 1 to day 168 ]
Percentage of patients with hospitalization due to respiratory-related events

•Length of hospital stay due to respiratory-related events [ Time Frame: Day 1 to day 168 ]
The number of days in length of hospital stay per patient due to respiratory-related events will be measured.

•Time to first usage of anti-pseudomonal antibiotic [ Time Frame: Day 1 to day 168 ]
Time to first usage of anti-pseudomonal antibiotic per patient will be assessed by number of days

•Percentage of patients who use anti-pseudomonal antibiotic [ Time Frame: Day 1 to day 168 ]
Percentage of patients who use anti-pseudomonal antibiotic will be assessed.

•Duration of use of anti-pseudomonal antibiotic [ Time Frame: Day 1 to day 168 ]
Number of days of use of anti-pseudomonal antibiotic per patient will be assessed.

•Change from baseline in tobramycin minimal inhibitory concentration for Pseudomonas aeruginosa [ Time Frame: Baseline and day 168 ]
Change from baseline in tobramycin minimal inhibitory concentration for Pseudomonas aeruginosa will be measured by laboratory testing.

Timepoint(s) of evaluation of this end point: Time Frame: Day 1 to day 168
Time Frame: Baseline and day 168

Secondary ID(s)

CTBM100CUS03

Source(s) of Monetary Support

Novartis Pharmaceuticals Corporation