An open-label clinical trial that evaluates the lung clearance index in cystic fibrosis patients = 6 years of age, chronically infected with Pseudomonas aeruginosa

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2014-001204-21-DE
• Date of registration: 22/08/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: An open-label clinical trial that evaluates the lung clearance index in cystic fibrosis patients = 6 years of age, chronically infected with Pseudomonas aeruginosa
• Scientific title: An 8 week open-label interventional multicenter study to evaluate the lung clearance index as endpoint for clinical trials in cystic fibrosis patients = 6 years of age, chronically infected with Pseudomonas aeruginosa
• Date of first enrolment: 17/11/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001204-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent 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):
a. quantitative pilocarpine iontophoresis sweat chloride test of greater than 60 mmol/L or 60 mEq/L
b. genotype with 2 identifiable CF-causing mutations
c. an abnormal nasal transepithelial potential difference characteristic of CF
3. Male and female patients 6 - 50 years of age at screening (Visit 1).
4. Patients with elevated LCI of = 7.5 at screening, confirmed by a central MBW specialist.
5. Patients with FEV1 of = 50% predicted at screening.
6. P. aeruginosa must be present in two sputum or deep cough throat swab cultures or bronchoalveolar lavage (BAL) (only for BAL, a threshold level of 103 CFU/mL is required) within 12 months prior to screening or in one culture within 12 months prior to screening and in the sputum or deep cough throat swab culture at screening.
7. Use of inhaled Tobramycin in a 28 days on / off regimen in the past 3 months before screening, as prescribed by the treating physician.
8. Clinically stable in the opinion of the investigator and likely to be able to participate in the study until the end of the study (Visit 5).


Are the trial subjects under 18? yes
Number of subjects for this age range: 17
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 and / or sputum culture yielding B. cenocepacia complex at screening (Visit 1).
2. Hemoptysis more than 60 mL at any time within 30 days prior to screening (Visit 1).
3. History of hearing loss or chronic tinnitus.
4. Serum creatinine 2mg/dL or greater, BUN 40 mg/dL or greater, known local or systemic hypersensitivity to aminoglycosides.
5. Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic during the study or in the past 56 days (8 weeks) prior to baseline visit (Visit 2).
6. Patients who have used oral or intravenous anti-pseudomonal antibiotics within 28 days prior to on-phase of study drug (Visit 2). These patients may be rescreened after 1 month following stop of i.v. treatment.
7. Change in dose, formulation or strength of the study drug in the past treatment cycle before screening.
8. Patients following onset or discontinuation of therapy with macrolides, chest physiotherapy, nebulized hypertonic saline, dornase alpha, long acting bronchodilators, inhaled steroids or inhaled mannitol during the study and within 56 days (8 weeks) prior to baseline visit (V2).
9. Use of loop diuretics within 7 days prior to first study medication administration (Visit 2).
10. Administration 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, regardless of whether there is evidence of local recurrence or metastases.
14. Patients with known or suspected neuromuscular disorders, e. g. Parkinson´s disease, Myasthenia gravis.
15. Patients or caregivers who are considered potentially unreliable or considered unlikely to be compliant within the trial.
16. 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 (> 5 mIU/mL).
17. Women who are menstruating and capable of becoming pregnant* and either not practicing a medically approved method of contraception (Pearl Index <1**) or not practicing total abstinence (when this is in line with the preferred and usual lifestyle of the patient) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion
*definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/mL or 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy
**examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe:
• hormonal oral contraception (Combination of estrogen and gestagen, PI=0.1-0.9)
• hormonal vaginal ring (combination of estrogen and gestagen, PI=0.65 uncorr.; 0.4 corr.)
• hormonal transdermal patch (combination of estrogen and gestagen PI= 0.72 uncorr.; 0.9 corr.)
• Estrogen-free ovulation inhibitors (containing desogestrel (PI=0.14)
• Implanted hormones containing etonogestrel (

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

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Chronic lung infection with Pseudomonas aeruginosa in cystic fibrosis patients
MedDRA version: 18.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 18.0 Level: LLT Classification code 10021860 Term: Infection Pseudomonas aeruginosa System Organ Class: 100000004862

Intervention(s)

Trade Name: TOBI Podhaler
Product Name: TOBI Podhaler
Product Code: TBM100C
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Tobramycin
CAS Number: 32986-56-4
Current Sponsor code: TBM100
Other descriptive name: TOBRAMYCIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 28-

Pharmaceutical Form: Nebulisation solution
INN or Proposed INN: Tobramycin
CAS Number: 3232986-56-4
Current Sponsor code: TBM100
Other descriptive name: TOBRAMYCIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Primary end point(s): Change of LCI after 4 weeks following onset of study drug inhalation versus Baseline

Secondary Objective: To assess:
• Change of FEV1 after 4 weeks following onset of study drug inhalation versus Baseline.
• Change in CFU after 4 weeks following onset of study drug inhalation versus Baseline
• Change of LCI after 1 week following onset of study drug inhalation versus Baseline.
• Change of LCI, FEV1 and CFU between week 4 (end of Study drug inhalation in the current treatment cycle) and week 8 (prior to start of Study drug inhalation in the following treatment cycle).
• Correlation between the changes of LCI, FEV1 and CFU after 1 week, 4 weeks, and 8 weeks versus Baseline, respectively.

Timepoint(s) of evaluation of this end point: 4 weeks

Main Objective: To assess the change of LCI after 4 weeks following onset of study drug inhalation versus Baseline

Secondary Outcome(s)

Secondary end point(s): 1 - Change of FEV1
2 - Change in CFU
3 - Change of LCI
4 - Change of LCI, FEV1 and CFU
5 - Correlation between the changes of LCI, FEV1 and CFU

Timepoint(s) of evaluation of this end point: 1- after 4 weeks following onset of study drug inhalation versus Baseline
2- after 4 weeks following onset of study drug inhalation versus Baseline
3- after 1 week following onset of study drug inhalation versus Baseline
4- between week 4 (end of Study drug inhalation in the current treatment cycle) and week 8 (prior to start of Study drug inhalation in the following treatment cycle).
5- after 1 week, 4 weeks, and 8 weeks versus Baseline, respectively.

Secondary ID(s)

CTBM100CDE02

Source(s) of Monetary Support

Novartis Pharma GmbH