Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase 3, Open-label, Randomized Trial to Evaluate the Safety and Efficacy of MP-376 Inhalation Solution (Aeroquin) vs. Tobramycin Inhalation Solution (TIS) in Stable CF Patients
Brief Summary: Patients with cystic fibrosis (CF) suffer from chronic infections of the lower respiratory tract that can be caused by one or multiple bacteria, including Pseudomonas aeruginosa, which has been particularly problematic to eradicate and been implicated as the major cause of morbidity and mortality in CF patients. Aerosol delivery of antibiotics directly to the lung increases the local concentrations of antibiotic at the site of infection resulting in improved antimicrobial effects compared to systemic administration. Bacterial resistance to current aerosol antibiotic treatments indicate a need for improved therapies to treat CF patients with pulmonary infections caused by multi-drug resistant Pseudomonas aeruginosa and other bacteria. High concentrations of MP-376 delivered directly to the lung are projected to have antimicrobial effects on even the most resistant organisms.


Options:
A: Inclusion Criteria:

* Successful completion of Core Study
* At least 6 years of age
* Males and females
B: 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
C: Inclusion Criteria:

* Documentation of CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

  * Sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test (QPIT);
  * Two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
  * Abnormal nasal potential difference.
* PA present in expectorated sputum or throat swab culture at Screening.
* FEV1 between (and including) 25% and 75% predicted at Screening.
* Negative pregnancy test at Screening.
* Ability to perform reproducible pulmonary function tests.
* Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.
* Ability to provide written informed consent.

Exclusion Criteria:

* Administration of antipseudomonal antibiotics by inhalation, IV, or oral routes (including azithromycin) within 14 days of Screening.
* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone/day or 20 mg prednisone every other day.
* History of sputum or throat swab culture yielding Burkholderia cepacia in the previous 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Administration of any investigational drug or use of any investigational device within 28 days of Screening and within 6 half-lives of the investigational drug (whichever was longer).
* Known local or systemic hypersensitivity to monobactam antibiotics.
* Inability to tolerate short-acting bronchodilator use at least three times daily.
* Changes in protocol-permitted antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days prior to Screening or between Screening and the next visit.
* Changes in physiotherapy technique or schedule within 7 days prior to Screening or between Screening and the next visit.
* History of lung transplantation.
* A chest x-ray indicating abnormal findings at Screening or within the previous 90 days.
* Abnormal renal or hepatic function at Screening.
* Any serious or active medical or psychiatric illness which, in the opinion of the investigator, would have interfered with participant treatment, assessment, or compliance with the protocol.
* Use of aerosolized hypertonic saline (except for sputum induction) during the 14 days preceding Visit 1.
D: Inclusion Criteria (selected):

* \> 12 years of age
* Confirmed Diagnosis of Cystic Fibrosis
* Positive sputum culture for P. aeruginosa within the past 12 months
* Patients are able to elicit an FEV1 \>/= 25% but \</= 85% of predicted value at screening
* Have received at least 3 courses of inhaled tobramycin over the preceding 12 months
* Clinically stable with no changes in health status within the last 28 days
* Able to reproducibly produce sputum and perform spirometry

Exclusion Criteria (selected):

* Use of any nebulized or systemic antibiotics within 28 days prior to baseline
* History of hypersensitivity to fluoroquinolones or inhaled or systemic aminoglycosides including tobramycin or any excipients
* Evidence of acute upper within 10 days or lower respiratory infections within 28 days prior to dosing
* CrCl \< 20 at Screening
* History of lung transplantation

Extension Portion of the Study: Patients enrolled in Mpex 209 are permitted to participate in the open label extension as long as they complete Visit 7 (Day 168), provide informed consent for participation in the open label extension of in the study and are clinically stable, as assessed by the Investigator.

Answer: D