A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo

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).

This study is designed to show how well tobramycin inhalation powder works and how safe it is when produced by a modified manufacturing process

Inclusion Criteria:

• Written informed consent given by adults or by the parents/legal guardian in combination with the patient's assent, if capable of assenting, before any assessment was performed

• Confirmed diagnosis of Cystic Fibrosis (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.

• Forced Expiratory Volume in one second (FEV1) at screening must have been ≥25% and ≤80% of normal predicted values for age, sex, and height based on Knudson criteria

• P. aeruginosa must have been 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 provide a deep throat cough swab at screening

• Able to comply with all protocol requirements

• 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

Exclusion Criteria:

• FEV1 at baseline (Visit 2) <25% or >80% of normal predicted values for age, sex, and height based on Knudson criteria, and/or FEV1 at baseline (Visit 2) deviated 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, blood urea nitrogen (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
• Initiation of treatment with dornase alfa within 28 days prior to study drug administration
• Initiation of treatment with inhaled steroids (or increased dose) within 28 days prior to study drug administration
• Initiation of treatment with inhaled hypertonic saline (HS) within 28 days prior to study drug administration
• 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 puretone 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 of evidence of local recurrence or metastases
• Patients with clinically significant laboratory abnormalities (not associated with the study indication) at screening
• Patients or caregivers with a history of noncompliance to medical regimens and patients or caregivers who are considered potentially unreliable
• Pregnant or nursing (lactating) women
• Women of child-bearing potential unless they used two reliable birth control methods

Other protocol-defined inclusion/exclusion criteria may apply