A clinical study to investigate long term safety of tobramycin inhalation powder (TIP) in patients with Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 3 February 2014
• Main ID: EUCTR2011-002000-32-HU
• Date of registration: 05/09/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A clinical study to investigate long term safety of tobramycin inhalation powder (TIP) in patients with Cystic Fibrosis
• Scientific 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
• Date of first enrolment: 25/11/2011
• Target sample size: 150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002000-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no 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

Countries of recruitment

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

Contacts

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

• Name: Public Information Desk
• Affiliation: Novartis Hungária Kft., Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provide written informed consent, HIPAA (Health Insurance Portability and Accountability Act) authorization (where applicable), and assent (as appropriate) 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 > 60 mmol/L,
• genotype with two identifiable CF-causing mutations,
• a positive newborn screening for CF,
• an abnormal nasal transepithelial potential difference characteristic of CF

3. Male and female patients = 6 years of age at screening (Visit 1).

4. FEV1 at screening (Visit 1) must be = 25% and =75% of normal predicted values for age, sex, and height based on the Knudson equation.

5. P aeruginosa must be present in a sputum/deep cough throat swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/ deepthroat cough swab culture at screening (Visit 1).

6. Able to comply with all protocol requirements.

7. Clinically stable in the opinion of the investigator.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
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 (B cc) complex within 2 years prior to screening and/or sputum culture yielding B cc. complex at screening (Visit 1).

2. Hemoptysis more than 60 mL at any time within 30 days prior to study drug administration (Visit 2).

3. History of hearing loss or chronic tinnitus deemed clinically significant by the investigator.

4. Serum creatinine 2 mg/dl or more, BUN 40 mg/dl or more, or an abnormal urinalysis defined as 2+ or greater proteinuria at screening (Visit 1).

5. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.

6. Patients who are regularly receiving more than 1 class of inhaled anti-pseudomonal antibiotic (inhaled anti-pseudomonal antibiotic are not allowed other than the study drug).

7. Any use of inhaled anti-pseudomonal antibiotics 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 (Visit 2).

9. Use of loop diuretics within 7 days prior to study drug administration (Visit 2).

10. Administration of any investigational drug within 30 days prior to enrollment (Visit 1) or 5 halflives, whichever is longer.

11. Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax.

12. History of malignancy of any organ system, treated or untreated, regardless of whether there is evidence of local recurrence or metastases.

13. Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening (Visit 1).

14. Patients with other clinically significant conditions (not associated with the study indication) at screening (Visit 1) which might interfere with the assessment of this study.

15. Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable.

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 hCG laboratory test (> 5 mIU/mL) at screening (Visit 1).

17. 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. 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 are considered not of child bearing potential if they have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.


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

Health Condition(s) or Problem(s) studied

Pseudomonas aeruginosa infection in cystic fibrosis patients
MedDRA version: 14.0 Level: LLT Classification code 10021860 Term: Infection pseudomonas aeruginosa System Organ Class: 10021881 - Infections and infestations

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

Intervention(s)

Trade Name: TOBI Podhaler 28 mg inhalációs por, kemény kapszula
Product Name: TIP (Tobramycin inhalation powder)
Product Code: TBM100C
Pharmaceutical Form: Inhalation powder, hard capsule
INN or Proposed INN: Tobramycin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 28-

Primary Outcome(s)

Primary end point(s): The incidence of treatment emergent adverse event

Main Objective: To assess the safety of TIP over 6 cycles of treatment in terms of the incidence of treatment emergent adverse events (AEs).

Secondary Objective: - To evaluate the safety profile of TIP in terms of acute change in FEV1

- To assess the efficacy of TIP over 6 cycles of treatment, as measured by the relative change in FEV1 , FVC and FEF25-75

- To assess the efficacy of TIP over 6 cycles of treatment, as measured by the absolute change in P. aeruginosa CFU in sputum.

- To evaluate the safety of TIP for P. aeruginosa tobramycin MIC as judged by change from baseline to the end of the dosing periods

- To evaluate the safety profile of TIP in terms of clinical laboratory results and, (in a subset of patients) audiology throughout the treatment period.

- To assess time to first and the rate of hospitalization due to serious respiratory-related AEs

- To assess the time to first and the rate of the usage of anti pseudomonal antibiotic (overall, oral, intravenous) over 6 cycles of TIP treatment other than pre-planned prophylactic treatment planned before enrolment.

Timepoint(s) of evaluation of this end point: over 6 cycles of treatment period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1) (Visit 2) => At Visit 3, Visit 5, Visit 7, Visit 9, Visit 11, Visit 13, Visit 14.

2) (Visit 2) => At Visit 3, Visit 5, Visit 7, Visit 9, Visit 11, Visit 13, Visit 14.

3) (Visit 2) => At Visit 3, Visit 5, Visit 7, Visit 9, Visit 11, Visit 13, Visit 14

4) over 6 cycles of treatment period

5) over 6 cycles of treatment period

6) At Visit 2, Visit 3, Visit 5, Visit 7, Visit 9, Visit 11, Visit 13.

7) Evaluation of clinical laboratory results and (in a sub-set of patients) audiology: over 6 cycles of treatment period

Secondary end point(s): 1) Relative change in FEV1 % predicted, FVC % predicted and FEF25-75 % predicted from baseline

2) Relative change in P aeruginosa CFU in sputum from baseline

3) Change in P aeruginosa tobramycin MIC from baseline

4) Rate of and time to the first hospitalization due to serious respiratory-related AE

5) Rate of and time to the first use of anti-pseudomonal antibiotics (overall, oral, intravenous)

6) Acute change in FEV% predicted from pre-dose to post-dose 30 minutes

7) Evaluation of clinical laboratory results and (in a sub-set of patients) audiology

Secondary ID(s)

CTBM100C2401

Source(s) of Monetary Support

Novartis Pharma Services AG