Please select the eligibility criteria that correspond to the clinical trial below.
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).
Brief 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


Options:
A: Inclusion Criteria:

* Male or female ≥12 years of age at Visit 1
* Enrolled in the CFFNPR (Patients may enroll in the Registry at Visit 1 if not previously enrolled.)
* Current hospitalization for treatment of a pulmonary exacerbation
* Planned hospital admission of at least 5 days with intravenous (IV) antibiotics at Visit 1
* Able to perform spirometry at admission and willing to perform spirometry on subsequent treatment and visit days
* Willing and able to complete symptom score daily
* Willing to return for a follow up visit at end of treatment (if necessary) and 28 days after start of IV antibiotic therapy
* Written informed consent (and assent when applicable) obtained from the participant or participant's legal representative

Exclusion Criteria:

* Previous enrollment in this study
* Treatment with IV antibiotics in the 6 weeks prior to Visit 1
* Admission to the intensive care unit for current pulmonary exacerbation
* Pneumothorax on admission
* Current hospitalization for scheduled pulmonary clean out
* Current hospitalization for sinusitis as the primary diagnosis
* Massive hemoptysis defined as \> 250 cc in a 24 hour period, or 100 cc/day over 4 consecutive days occurring within one week of Visit 1
* Current pulmonary exacerbation thought to be due to allergic bronchopulmonary aspergillosis (ABPA)
* Ongoing treatment with prednisone equivalent \>10 mg/day for greater than 2 weeks initiated prior to Visit 1
* History of solid organ transplantation Currently receiving antimicrobial therapy to treat non-tuberculous mycobacterium (e.g., M. abscessus, M. avium complex)
B: Inclusion Criteria:

* Written informed consent obtained from patient or designated legal guardian prior to the performance of any study related procedures.
* Male or female study subjects ≥6 years of age or older
* Confirmed diagnosis of CF
* History of chronic infection with P. aeruginosa
* Study subjects must produce a screening specimen that is positive for growth of P. aeruginosa
* FEV1 ≥ 40% predicted at Screening
* SaO2 ≥ 90% at Screening while breathing room air
* Ability to comply with study medication use, study visits and study procedures as judged by the investigator
* Ability to produce sputum or be willing to undergo an induction to produce sputum for clinical evaluation
* Clinically stable with no evidence of acute upper or lower respiratory tract infection of history of pulmonary exacerbation within 4 weeks prior to screening

Key Exclusion Criteria:

* Administration of any investigational drug within 8 weeks prior to Screening
* Emergency room visit or hospitalization for CF or respiratory-related illness within 4 weeks prior to screening
* History of alcohol, medication or illicit drug abuse within the 1 year prior to screening
* History of lung transplant
* Female of childbearing potential who is lactating or is not practicing an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD)
* Positive pregnancy test
* Use of any anti-pseudomonal anitbiotics (IV antibiotics, all inhalation antibiotics, oral fluoroquinolones)within the 28 days prior to screening
* Initiation of chronic therapy (i.e. TOBI®, high-dose ibuprofen, rhDNase, macrolide antibiotics) within 28 days prior to screening
* History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of Screening
* History of mycobacterial or Aspergillus infection
* Requiring treatment within 2 years prior to screening, and/or history of allergic bronchopulmonary aspergillosis.
* History of biliary cirrhosis with portal hypertension, or splenomegaly
* History of daily, continuous oxygen supplementation or requirement for more than 2 L/min at night Change in chest x-ray at screening (or within the 3 months prior to screening)
C: Inclusion Criteria:

* Male or female ages less than or equal to 12 years.
* Diagnosis of CF based upon the criteria established by the 1997 CF Consensus Conference: (i) sweat chloride \> 60 mEq/L by quantitative pilocarpine iontophoresis; or (ii) genotype with two identifiable mutations consistent with CF; or (iii) an abnormal nasal transepithelial potential difference, and (iv) one or more clinical features consistent with CF.
* No prior isolation of Pa from respiratory cultures (1 or more cultures in 24 months prior to enrollment), or, if prior isolation of Pa from respiratory cultures, at least a two-year history of Pa negative cultures (1 or more cultures/year), or concurrently enrolled in the EPIC Clinical Trial.
* Signed informed consent to participate in data submission to the CFF National Patient Registry.
* Signed informed consent by parent or legal guardian.
D: 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

Answer: D