Chronic lung infection with Pseudomonas aeruginosa in cystic fibrosis patients MedDRA version: 17.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 17.1 Level: LLT Classification code 10021860 Term: Infection Pseudomonas aeruginosa
Conditions
Interventions
Trade Name: TOBI Podhaler
Product Name: TOBI Podhaler
Product Code: TBM100C
Pharmaceutical Form: Inhalation powder, hard capsule
INN or
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provide written informed consent, Health Insurance Portability and Accountability Act (HIPAA) authorization (where applicable), and assent (as appropriate for minors) prior to the performance of any study-related procedure 2.Confirmed diagnosis of CF by one or more of the following tests for CF (current or historic):•quantitative pilocarpine iontophoresis sweat chloride test of greater than 60 mmol/L or 60 mEq/L•genotype with identifiable CF-causing mutations on both chromosomes•a positive newborn screening for CF•an abnormal nasal transepithelial potential difference characteristic of CF 3.Male and female patients 6 years of age or older at screening (Visit 1) 4.FEV1 at screening (Visit 1) must be at least 25% and less than or equal to 90% of normal predicted values for age, sex, and height based on the NHANES III values (Hankinson et al 1999) for patients 18 years of age or greater, and based on values from Wang (Wang et al 1993) for patients less than 18 years of age. Please refer to Appendix 4 for the relevant equations. 5.Documented use of any of the inhaled antibiotics to treat chronic P. aeruginosa infection based on local practice:•TIS, colistimethate, or TIP for at least 1 cycle (4 weeks on treatment followed by 4 weeks off treatment) within the last 6 months or•colistimethate continuous use for at least 8 weeks within the last 6 monthsThis cycle of treatment (or continuous colistimethate treatment period) is in addition to the treatment cycle during which the subject is being screened. 6.P. aeruginosa must be present in a sputum or deep cough throat swab culture or bronchoalveolar lavage (BAL) (only for BAL a threshold level of 10^3 CFU/mL is required) within 6 months prior to screening and in the sputum or deep cough throat swab culture at screening or rescreening (Visit 1) 7.Judged by the investigator to be able to use the dry powder inhaler successfully 8.Clinically stable in the opinion of the investigator Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 37 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.History of sputum culture or deep cough throat swab (or BAL) culture yielding Burkholderia cenocepacia complex within 2 years prior to screening or sputum culture yielding B. cenocepacia complex at screening (Visit 1) 2.Hemoptysis more than approx. 60 mL at any time within 30 days prior to screening 3.History of hearing loss or chronic tinnitus deemed clinically significant by the investigator 4.Serum creatinine 176.8 µmol/L (2 mg/dL) or greater, blood urea nitrogen (BUN) 14.28 µmol/L (40 mg/dL) or greater or an abnormal urinalysis defined as 2+ or greater proteinuria at screening (Visit 1) 5.Known local or systemic hypersensitivity to aminoglycosides 6.Regularly receiving more than 1 class of inhaled antipseudomonal antibiotic. During the study, inhaled antipseudomonal antibiotics are not allowed other than the antipseudomonal antibiotic the patient is using atthe time of entrance into the study. 7.Use of systemic antipseudomonal antibiotics within 28 days prior to study medication administration (Visit 2) 8.For patients on colistimethate: current use of cautioned concomitant medications as indicated in the prescribing information, including aminoglycosides, polymixins, curariform muscle relaxants (e.g. tubocurarine), ether, succinylcholine, gallamine, decamethonium, and sodium citrate, at screening 9.Use of loop diuretics within 7 days prior to study medication administration (Visit 2) 10.Use of any investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening (Visit 1) 11.Signs and symptoms of acute pulmonary disease, e.g. pneumonia, pneumothorax 12.Body mass index less than 12 kg/m2 13.History of malignancy of any organ system, treated or untreated 14.Clinically significant laboratory abnormalities (not associated with the study indication) at screening (Visit 1) 15.Clinically significant conditions or findings at screening (Visit 1) that might interfere with the accurate and valid assessment of this study 16.Patients or caregivers who are considered potentially unreliable or considered unlikely to be compliant within the trial 17.Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test 18.Women of childbearing 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. The two methods can be a double barrier method or a barrier method plus a hormonal method. •Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge, or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent. •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare as a primary indicator for ease of use the mean cumulative time required to set-up the delivery device (including preparation of the treatment), administer the drug, and clean the delivery device for TIP administered with the T 326 Inhaler with the cumulative time to performthe same activities (including disinfection of the device, where applicable) for the patient's usual (pre-study prescribed) nebulized, antibiotic treatment for P. aeruginosa.; Secondary Objective: To assess: -the absolute change in the number of P.aeruginosa colony-forming unitsin sputum after up to a period of 28days of treatment in each treatment arm -the frequency and type of microbial contamination of the T-326 Inhaler used to administer TIP after lifetime use(7days of treatment) compared with the contamination of the nebulizer used for the patient's usual nebulized antibiotic treatment for P.aeruginosa or for any other nebulized medication at baseline(Visit2)and at each visit. - tolerability and safety of TIPvsTISvscolistimethate over both the on-treatment and off-treatment periods of the study by comparison of adverse event rates, severity, and discontinuation rates To evaluate: -the change in the minimum inhibitory concentration of the relevant antibiotic for P. aeruginosa after a period of up to 28days of treatment ofTIPvsTISvscolistimethate -the safety profile of TIPvsTISvscolistimethate in terms of clinical laboratory results and postinhalational bronchospasm ;Primary end point(s): Total time for administration of TIP with the Podhaler compared to the total time for administration of TIS or colistimethate with nebulisers;Timepoint(s) of evaluation of this end point: 7 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Number of P. aeruginosa colony forming units (CFU) 2- Frequency of microbial contamination of the T-326 Inhaler (Podhaler) compared with the contamination of the nebulizer used for the patient's usual nebulised antibiotic 3- Averse event (AE) rates after each treatment cycle 4- Change in the minimum inhibitory concentration (MIC) of the relevant antibiotic for P. aeruginosa 5- Clinical laboratory results for TIP vs TIS and colistimethate after upto 28 days of treatment 6- Type of microbial contamination of the T-326 Inhaler (Podhaler) compared with the contamination of the nebulizer used for the patient's usual nebulised antibiotic after upto 28 days of treatment in each treatment period ; Timepoint(s) of evaluation of this end point: 1- 28 days post-treatment 2- 28 days post-treatment 3- 168 days 4- 28 days post-treatment 5- 28 days post-treatment 6- 28 days post-treatment | — |
Countries
Germany, Ireland, Spain, Switzerland, United Kingdom
Contacts
Public ContactMedical Information Services
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed