Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Open-Label, Active-Controlled, Multicenter Study to Assess the Efficacy, Safety and Tolerability of Arikayce™ in Cystic Fibrosis Patients With Chronic Infection Due to Pseudomonas Aeruginosa
Brief Summary: A major factor in the respiratory health of Cystic Fibrosis (CF) participants is the prevalence of chronic Pseudomonas aeruginosa (Pa) infections. The Pa infection rate in CF patients increases with age and by age 18 years approximately 85% of CF patients in the US are infected. Liposomal amikacin for inhalation (Arikayce™) was developed as a possible treatment for chronic infection due to Pa in CF patients.

The purpose of this study is to determine whether Arikayce™ is effective in treating chronic lung infections caused by Pa in CF participants. The effectiveness, safety, and tolerability of Arikayce™ will be compared to Tobramycin TOBI®, an inhalation antibiotic already available for use.


Options:
A: Key Inclusion Criteria:

* Written informed consent or assent
* Confirmed diagnosis of CF
* History of chronic infection with Pseudomonas aeruginosa
* Sputum culture positive for Pseudomonas aeruginosa at Screening
* FEV1 ≥ 25% of predicted value at Screening

Key Exclusion Criteria:

* FEV1 \<25% of predicted at Screening
* History of major complications of lung disease within 8 weeks prior to Screening
* Hemoptysis of ≥60 mL in a 24-hour period within 4 weeks prior to Screening
* History of positive culture for Burkholderia cepacia within 2 years prior to Screening
* History of pulmonary tuberculosis or non-tuberculous mycobacterial lung disease treated within 2 years prior to Screening or requiring treatment at the time of screening
* History of Allergic Broncho-Pulmonary Aspergillosis or any other condition requiring systemic steroids at a dose ≥ equivalent of 10 mg/day of prednisone within 3 months prior to Screening
* Presence of any clinically significant cardiac disease
* History of lung transplantation
* Daily, continuous oxygen supplementation or nighttime supplemental oxygen requirement of greater than 2 L/min
* Administration of any investigational products within 8 weeks prior to study Day 1
* Smoking tobacco or any substance within 6 months prior to screening or anticipated inability to refrain from smoking throughout the study
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:

* 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)

Answer: A