A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder after Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who successfully Completed Participation in Study CTBM100C2303E1.

• Register: EUCTR
• Last refreshed on: 29 October 2012
• Main ID: EUCTR2009-016734-26-EE
• Date of registration: 15/12/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder after Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who successfully Completed Participation in Study CTBM100C2303E1.
• Scientific title: A Phase III Open-Label Extension Study to Assess the Safety and Efficacy of Tobramycin Inhalation Powder after Manufacturing Process Modifications (TIPnew) in Cystic Fibrosis (CF) Patients Who successfully Completed Participation in Study CTBM100C2303E1.
• Date of first enrolment: 08/01/2010
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016734-26
• 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

Countries of recruitment

Bulgaria, Estonia, Latvia, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed consent given by adult patients or by the parents/legal guardian on behalf of the patient in combination with the patient’s assent, if capable of assenting, before any assessment is performed.
2. Successfully completed all visits in study CTBM100C2303 and CTBM100C2303E1 including visit 11, which should have taken place not more than 5 days before enrollment into this study.
3. Able to comply with all protocol requirements.
4. Use of an effective means of contraception in females of childbearing potential.
5. Clinically stable in the opinion of the investigator to be treated according to this protocol

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) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any use of inhaled or systemic anti-pseudomonal antibiotics between the termination visit of CTBM100C2303E1 and enrollment into this study. (Use of inhaled antipseudomonal antibiotics other than study drug is not allowed between start of study drug administration and follow-up/termination. Use of systemic antibiotics between start of study drug administration and follow-up/termination is at the investigator’s discretion).
2. Serum creatinine 2 mg/dl or above, BUN 40 mg/dl or above, or an abnormal urinalysis defined as 2+ or greater proteinuria.
3. Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
4. Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax.
5. Administration of any investigational drug within 30 days prior to enrollment (except for study medication in CTBM100C2303 and CTBM100C2303E1).
6. Any previous exposure to tobramycin dry powder for inhalation (TIP), with the exception of study medication for study CTBM100C2303 and CTBM100C2303E1.
7. Administration of loop diuretics (such as Furosemide and Bumetanide) within 7 days prior to study drug administration.
8. Initiation of chronic macrolide therapy between the termination visit of CTBM100C2303E1 and enrollment into this studystudy (the dosage/regimen must remain stable throughout the study).
9. Initiation of treatment with dornase alpha between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study).
10. Initiation of treatment with inhaled steroids (or increased dose) between the termination visit of CTBM100C2303E1 and enrollment into this study (the dosage/regimen must remain stable throughout the study).
11. Initiation of treatment with inhaled hypertonic saline (HS) between the termination visit of CTBM100C2303E1 and enrollment into this study. In addition, patients should be instructed to inhale their HS at least 30 minutes before their pulmonary function tests (PFT). Patients should be consistent with the timing of taking their HS at home or clinic, prior to their PFT.
12. Personal history of abnormal hearing or family history of abnormal hearing other than typical hearing loss associated with the aging process.
13. Abnormal result from any audiology testing (defined as either a unilateral pure-tone audiometry test showing a threshold elevation > 20 dB at any frequency across the frequency range 0.25 kHz to 8 kHz or the absence of emission at the evoked otoacoustic emission test).
14. History of sputum culture or throat swab (or BAL) culture yielding Burkholderia cepacia (B.cepacia) within 2 years prior to screening for CTBM100C2303E2 or at enrollment into this study.
15. Hemoptysis of more than 60 mL at any time within 30 days prior to study drug administration.
16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
17. Patients with clinically significant laboratory abnormalities (unless expected under the study indication).
18. Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable.
19. 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 tes

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: 12.0 Level: LLT Classification code 10021860 Term: Infection pseudomonas aeruginosa

Intervention(s)

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): Adverse events from time of first administration of study drug until study completion.

Secondary Objective: • To evaluate the efficacy of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) for the treatment of infections with P. aeruginosa in patients suffering from cystic fibrosis, assessed by FEV1 , FVC and FEF 25-75 profile.
• To assess the effect of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) on the density of microorganisms in sputum samples of patients.

Main Objective: To evaluate the safety profile of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) for the treatment of infections with P. aeruginosa in patients suffering from cystic fibrosis, over three additional treatment cycles.

Secondary ID(s)

CTBM100C2303E2