a study of tobramycin inhalation powder from a modified manufacturing process versus placebo

Conditions: Cystic Fibrosis

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


Eligibility criteria:
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) \ 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

Keywords: tobramycin inhalation powder cystic fibrosis lung diseases anti-bacterial agents treatment of infections with p. aeruginosa in cystic fibrosis subjects