Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Cystic Fibrosis
Brief Summary: In some participants with cystic fibrosis (CF), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the cystic fibrosis transmembrane regulator (CFTR) protein. Ataluren has been shown to partially restore CFTR production in animals with CF due to a nonsense mutation. The main purpose of this study is to understand whether ataluren can safely increase functional CFTR protein in the cells of participants with CF due to a nonsense mutation.


Options:
A: Inclusion Criteria: Participants must meet all of the following conditions to be eligible for enrollment into the study:

1. Diagnosis of CF based on conclusively abnormal sweat test (sweat chloride \>35 milliequivalents \[mEq\]/liter).
2. Abnormal nasal epithelial TEPD total chloride conductance (a more electrically negative value than 5 mV for Δchloride-free+isoproterenol).
3. Presence of a mutation in both alleles.
4. Documentation that a blood sample has been drawn for reconfirmation of the presence of a nonsense mutation in the CFTR gene.
5. Age ≥6 years.
6. Body weight ≥25 kg.
7. FEV1 ≥40% of predicted for age, gender, and height.
8. Oxygen saturation ≥92% on room air.
9. Willingness of male and female participants, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and follow-up periods.
10. Negative pregnancy test (for females of childbearing potential).
11. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures (including TEPD measurements, clinical laboratory tests, pulmonary function tests, and PK sampling), and study restrictions.
12. Ability to provide written informed consent and/or assent.
13. Evidence of signed and dated informed consent document (by the participant or a legal guardian) indicating that the participant and/or the legal guardian has been informed of all pertinent aspects of the trial.

Exclusion Criteria: The presence of any of the following conditions will exclude a participant from enrollment in the study:

1. Prior exposure to ataluren.
2. Prior or ongoing medical condition (for example, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
3. Ongoing acute illness including acute upper or lower respiratory infections within 2 weeks before start of study treatment.
4. History of major complications of lung disease (including recent massive hemoptysis or pneumothorax) within 2 months prior to start of study treatment.
5. Abnormalities on screening chest x-ray suggesting clinically significant active pulmonary disease other than CF, or new, significant abnormalities such as atelectasis or pleural effusion which may be indicative of clinically significant active pulmonary involvement secondary to CF.
6. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test.
7. Hemoglobin \<10 grams/deciliter (g/dL).
8. Serum albumin \<2.5 g/dL.
9. Abnormal liver function (serum total bilirubin \> the upper limit of normal, or serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) \>2.0 times the upper limit of normal).
10. Abnormal renal function (serum creatinine \>1.5 times upper limit of normal).
11. Pregnancy or breast-feeding.
12. History of solid organ or hematological transplantation.
13. Exposure to another investigational drug within 14 days prior to start of study treatment.
14. Ongoing participation in any other therapeutic clinical trial.
15. Ongoing use of thiazolidinedione peroxisome proliferator-activated receptor gamma (PPAR γ) agonists, for example, rosiglitazone (Avandia® or equivalent) or pioglitazone (Actos® or equivalent).
16. Change in intranasal medications (including use of corticosteroids, cromolyn, ipratropium bromide, phenylephrine, or oxymetazoline) within 14 days prior to start of study treatment.
17. Change in treatment with systemic or inhaled corticosteroids within 14 days prior to start of study treatment.
18. Use of or requirement for inhaled gentamicin or amikacin within 14 days prior to start of study treatment or during study treatment.
19. Requirement for systemic aminoglycoside antibiotics within 14 days prior to start of study treatment.
B: Inclusion Criteria:

* Participants from Study 110 or Study 111 entering the ivacaftor arm must have completed the assigned study drug treatment duration in the previous study.
* Participants from Study 113 entering the ivacaftor arm must have completed all study related treatments through the Follow-up Visit and met the Study 113 responder criteria during the previous study.
* Participants entering the observational arm must have completed at least 4 weeks of study drug treatment in their previous study (Study 110 or Study 111), must have completed the previous study but do not wish to enroll in the ivacaftor arm, or must have completed the previous study but do not meet the inclusion criteria of the ivacaftor arm.
* Participants of childbearing potential entering the ivacaftor arm must not be pregnant.
* Participants entering the ivacaftor arm must be willing to comply with contraception requirements.

Exclusion Criteria (Ivacaftor Arm Only):

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the Participant.
* Use of moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A.
* Evidence of cataract or lens opacity at or before the Day 1 Visit.
C: Inclusion Criteria:

* Male or female with confirmed diagnosis of CF
* Must have at least 1 allele of the R117H CFTR mutation
* Percent predicted forced expiratory volume in 1 second (FEV1) 40 percent (%) to 90% (for subjects aged 12 years or older) or 40% to 105% (for subjects aged 6 to 11 years) predicted normal for age, sex, and height
* 6 years of age or older
* Minimum weight of 15 kilogram (kg) at screening
* Females of childbearing potential must not be pregnant
* Willing to comply with contraception requirements

Exclusion Criteria:

* CFTR gene mutation leading to CFTR channel with gating defect (that is, any 1 of the following mutations: G551D, G178R, G551S, S549N, S549R, G970R, G1244E, S1251N, S1255P, or G1349D)
* History of any illness or condition that might confound the results of the study or pose an additional risk in administering ivacaftor to the subject
* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before the first dose of study drug
* Abnormal liver function, at screening, defined as greater than or equal to (\>=) 3 time upper limit of normal (ULN), of any 3 or more of the following: serum aspartate transaminase (AST), serum alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), serum alkaline phosphatase (ALP), total bilirubin
* Colonization with organisms associated with a more rapid decline in pulmonary status (for example, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening
* History of solid organ or hematological transplantation
* History of alcohol, medication or illicit drug abuse within 1 year before the first dose of study drug
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days before screening
* Any "non-CF-related" illness within 2 weeks before Day 1 (first dose of study drug). "Illness" was defined as an acute (serious or non-serious) condition (for example, gastroenteritis)
* Use of any inhibitors or inducers of cytochrome (CYP) P450 3A
D: Inclusion Criteria:

* Weighing at least 15 kg
* Confirmed diagnosis of cystic fibrosis (CF) and G551D mutation in at least 1 allele
* Forced expiratory volume in 1 second (FEV1) of 40% to 105% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at Screening
* Able to swallow tablets
* As judged by the investigator, parent or legal guardian and subject must have been able to understand protocol requirements, restrictions, and instructions, and the parent or legal guardian should have been able to ensure that the subject complied with, and was likely to complete, the study as planned
* Parent or legal guardian must have signed the informed consent form and corresponding assent must be obtained from the subject
* Willing to use at least 1 highly effective birth control method during the study
* No clinically significant abnormalities that would have interfered with the study assessments, as judged by the investigator

Exclusion Criteria:

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
* Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 of the study
* Abnormal liver function ≥ 3x the upper limit of normal
* Abnormal renal function at Screening
* History of solid organ or hematological transplantation
* Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within 30 days prior to Screening
* Use of inhaled hypertonic saline treatment
* Concomitant use of any inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4)

Answer: A