A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase III Study in Cystic Fibrosis (CF) Subjects to Assess Efficacy, Safety and Pharmacokinetics of Tobramycin Inhalation Powder from a Modified Manufacturing Process (TIPnew).

• Register: EUCTR
• Last refreshed on: 29 May 2012
• Main ID: EUCTR2008-002318-22-LT
• Date of registration: 22/01/2009
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase III Study in Cystic Fibrosis (CF) Subjects to Assess Efficacy, Safety and Pharmacokinetics of Tobramycin Inhalation Powder from a Modified Manufacturing Process (TIPnew).
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase III Study in Cystic Fibrosis (CF) Subjects to Assess Efficacy, Safety and Pharmacokinetics of Tobramycin Inhalation Powder from a Modified Manufacturing Process (TIPnew).
• Date of first enrolment: 07/09/2009
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002318-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, Estonia, Latvia, Lithuania

Key inclusion & exclusion criteria

Inclusion criteria:
Main inclusion criteria (refer to full protocol for comprehensive list)
• Confirmed diagnosis of CF by the presence of one or more clinical features of CF in addition to: - a quantitative pilocarpine iontophoresis sweat chloride test of > 60 mEq/L; or - identification of well-characterized disease-causing mutations in each CFTR gene; or - an abnormal nasal transepithelial potential difference characteristic of CF.
• Male and female subjects aged 6 years to 21 years of age at the time of screening.
• FEV1 at screening must be >= 25% and <= 80% of normal predicted values for age, sex, and height based on Knudson criteria.
• P. aeruginosa must be present in a sputum/deep-throat cough swab culture (or bronchoalveolar lavage [BAL]) within 6 months prior to screening and in the sputum/
deep-throat cough swab culture at the screening visit.
• Able to expectorate a sputum sample or to provide a deep-throat cough swab at screening.
• Use of an effective means of contraception in females of childbearing potential.
• 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:
Main exclusion criteria (refer to full protocol for comprehensive list)
• FEV1 at baseline (visit 2) is < 25% or > 80% of normal predicted values for age, sex, and height based on Knudson criteria, and/or FEV1 at baseline (visit
2) deviates by >= 10% from the FEV1 measured at screening (visit 1).
• Any use of inhaled anti-pseudomonal antibiotics within 4 months prior to screening.
• Any use of systemic anti-pseudomonal antibiotics within
28 days prior to study drug administration.
• Serum creatinine 2 mg/dl or above, BUN 40 mg/dl or above, or an abnormal urinalysis defined as 2+ or greater proteinuria.
• Known local or systemic hypersensitivity to aminoglycosides or inhaled antibiotics.
• Signs and symptoms of acute pulmonary disease, e.g., pneumonia, pneumothorax.
• Administration of any investigational drug within 30 days prior to enrollment.
• Any previous exposure to tobramycin dry powder for inhalation (TIP).
• Administration of loop diuretics within 7 days prior to study drug administration.
• Initiation of treatment with chronic macrolide therapy within 28 days prior to
study drug administration (subjects may be taking chronic macrolide therapy at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration and the dosage/regimen must remain stable throught the study)
• Initiation of treatment with dornase alpha within 28 days prior to study drug administration (subjects may be taking dornase alpha at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration and the dosage/regimen must remain stable throught the study).
• Initiation of treatment with inhaled steroids (or increased dose) within 28 days prior to study drug administration (subjects may be taking inhaled steroids at the time of enrollment into CTBM100C2303, but they must have initiated treatment more than 28 days prior to study drug administration and the dosage/regimen must remain stable throught the study).
• Initiation of treatment with inhaled hypertonic saline (HS) within 28 days prior to study drug administration (subjects may be inhaling hypertonic saline at the time of enrollment into CTBM100C2303, butthey must have initiated treatment more than 28 days prior to study drug administration and must be on a stable regimen). 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 respect to the timing of taking their HS at home or clinic, prior to their PFT.
• Personal history of abnormal hearing or family history of abnormal hearing other than typical hearing loss associated with the aging process.
• Known 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).
• History of sputum culture or throat swab (or BAL) culture yielding Burkholderia cepacia (B. cepacia) within 2 years prior to screening and/or sputum culture yielding B. cepacia at screening.
• Hemoptysis of more than 60 mL at any time within 30 days prior to study drug administration.
• 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


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: 9.1 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
Other descriptive name: TBM100C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 28-
Pharmaceutical form of the placebo: Inhalation powder, hard capsule
Route of administration of the placebo: Inhalation use

Primary Outcome(s)

Main 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 cystic fibrosis subjects, assessed by relative change from baseline FEV1 percent predicted to day 29, compared to placebo.

Primary end point(s): Relative change in FEV1 percent predicted from baseline to day 29

Secondary 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 cystic fibrosis subjects, compared to placebo.
• To assess the pharmacokinetic properties of tobramycin from TIPnew.
• To assess the effect of tobramycin inhalation powder after modifications in the manufacturing process (TIPnew) on the density of microorganisms in sputum samples of subjects.

Secondary ID(s)

CTBM100C2303