A Study of Tobramycin Inhalation Powder From a Modified Manufacturing Process Versus Placebo
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Respiratory Aspiration; Fibrosis
Intervention: Tobramycin Inhalation Powder; Placebo
Intervention description: Tobramycin Inhalation Powder as produced by a modified manufacturing process TIP. TIP was provided in hard capsules each containing 28 mg active ingredient (tobramycin); Capsules were packaged in blister cards and administered by the T-326 Inhaler.; Placebo inhalation powder consisting of the excipients used for TIP. Placebo was provided in hard capsules, containing 20 mg placebo powder, which were packaged in blister cards, matching in appearance to TIP. Capsules were administered by the T-326 Inhaler.
Intervention MeSH terms: Tobramycin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 62.0
Sex: All
Minimum age: 6 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Tobramycin Inhalation Powder; Cystic fibrosis; Lung diseases; Anti-Bacterial Agents; Treatment of infections with P. aeruginosa in cystic fibrosis subjects

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) <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