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 (selected):

* \> 16 years of age
* Confirmed Diagnosis of Cystic Fibrosis
* Positive sputum culture for P. aeruginosa within the past 18 months
* Patients are able to elicit a forced expiratory volume in 1 second (FEV1) \>/= 25% but \</= 85% of predicted value at screening
* Have received at least 3 courses of inhaled antimicrobials over the preceding 12 months
* Clinically stable with no changes in health status within the last 30 days
* Able to reproducibly produce sputum and perform spirometry

Exclusion Criteria (selected):

* Use of any nebulized or systemic antibiotics within 30 days prior to baseline
* History of hypersensitivity to fluoroquinolones or intolerance with aerosol medication
* Evidence of acute upper within 10 days or lower respiratory infections within 30 days prior to dosing
* Creatine clearance \< 50mg/ml, aspartate transaminase (AST), alanine transaminase (ALT) or total bilirubin \>/= 3 x upper limit of normal (ULN) at Screening
B: Inclusion Criteria:

* Patients of either sex aged ≥ 6;
* Clinical diagnosis of cystic fibrosis defined as: (1)Patients preferably registered in the National Registry of CF (or other documents depending on country legislation); (2) Evidence of two or more typical pulmonary clinical features observed in CF, e.g., persistent colonization/infection with typical CF pathogens, chronic cough and sputum production, persistent chest radiography abnormalities, airway obstruction, nasal polyps and/or digital clubbing;
* Positive response in the standard sweat test (sweat chloride concentration ≥ 60 mmol/l for the standard method or ≥ 80 mmol/L for a microduct technique) documented in the clinical records and/or gene mutation documented in the clinical records;
* Chronic colonization of P. aeruginosa: presence in a sputum or throat culture of a minimum of 2 positive samples for P. aeruginosa over the previous 12 months and/or presence of more than two precipitating antibodies against P. aeruginosa;
* Sputum containing P. aeruginosa susceptible to tobramycin (defined as a zone diameter ≥ 16 mm after testing with 10 µg tobramycin disk or as a minimal inhibition concentration based on microdilution testing system) as identified by local laboratory at screening visit;
* Forced expiratory volume in 1 sec (FEV₁) ≥ 40% and ≤ 80% of the predicted normal value;
* Written informed consent obtained by parents/legal representative according to local regulations) and by the patient (when appropriate).

Exclusion Criteria:

* Administration of antipseudomonal antibiotic therapy by any route in the previous 4 weeks;
* Evidence of impaired renal function (serum creatinine level ≥ 1.5 mg/dl);
* Evidence of impaired auditory function (auditory threshold in either ear above 20 dB at frequencies between 250 and 8000Hz);
* Sputum culture containing Burkholderia cepacia;
* Patients with end-stage lung disease, candidates for heart-lung transplantation;
* History of other clinically significant cardiac, renal, neurological, gastrointestinal, hepatic or endocrine disease related to cystic fibrosis, whose sequelae and/or treatment can interfere with the results of the present study;
* Female subjects: pregnant or with active desire to be pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (i.e., contraceptive methods other than rod containing a hormone that prevents user from getting pregnant and that will be placed under the skin, syringes that contain a contraceptive hormone, combined birth control pill, i.e., such that contains two hormones, some intrauterine devices (IUDs) and sexual abstinence). A pregnancy test in urine is to be carried out in women of a fertile age at screening and at the last clinic visit;
* Known hypersensitivity to aminoglycosides;
* Patients with evidence of alcohol or drug abuse, likely to be not compliant with the study protocol or likely to be not compliant with the study treatments;
* Participation in another clinical trial with an investigational drug in the four weeks preceding the screening visit.
C: 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)
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