Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Open-label Study Evaluating the Long-term Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis
Brief Summary: This study evaluated the long-term safety and tolerability of elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA) triple combination (TC) treatment in participants with cystic fibrosis (CF).


Options:
A: Inclusion Criteria:

1. Male or female subject ≥ 18 years of age, on the day of signing the Informed Consent Form (ICF).
2. A confirmed clinical diagnosis of CF.
3. One F508del mutation on one allele in the CFTR gene, a gating (class III) mutation (one of the following: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R) on the 2nd allele in the CFTR gene (documented in the subject's medical record or CF registry).
4. Weight ≥ 40 kg.
5. Stable concomitant treatment for at least 4 weeks (28 days) prior to baseline (including physician prescribed ivacaftor (Kalydeco®) 150 mg b.i.d.).
6. Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted normal for age, gender and height at screening (pre- or postbronchodilator).

Exclusion Criteria:

1. History of clinically meaningful unstable or uncontrolled chronic disease that makes the subject unsuitable for inclusion in the study in the opinion of the investigator.
2. Unstable pulmonary status or respiratory tract infection (including rhinosinusitis) requiring a change in therapy within 4 weeks of baseline.
3. Need for supplemental oxygen during the day, and \>2 liters per minute (LPM) while sleeping.
4. History of hepatic cirrhosis with portal hypertension (e.g., signs/symptoms of splenomegaly, esophageal varices, etc).
5. Abnormal liver function test at screening; defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or alkaline phosphatase and/or total bilirubin (\>1.5 times ULN (CTCAE Grade 2) and/or gamma-glutamyl transferase (GGT) ≥ 3x the upper limit of normal (ULN), and/or total bilirubin (\>1.5 times ULN (CTCAE Grade 2).
6. Estimated creatinine clearance \< 60mL/min using the Cockroft-Gault formula at screening.
B: Inclusion Criteria:

* Currently participating in study VX17-659-105 (NCT03447262)

Exclusion Criteria:

* History of drug intolerance in study VX17-659-105 that would pose an additional risk to the participant in the opinion of the investigator
* Current participation in an investigational drug trial (other than study VX17-659-105)

Other protocol defined Inclusion/Exclusion criteria may apply.
C: Inclusion Criteria:

1. Able to communicate with pertinent staff, able to understand and willing to comply with the requirements of the trial, and able and willing to give informed consent.
2. Willing to practice a reliable and study-accepted method of contraception during the study.
3. Diagnosis of cystic fibrosis consisting of both:

   1. clinical manifestations of cystic fibrosis and
   2. either cystic fibrosis genotype heterozygous for Delta F508 with a second identified CFTR mutation, or cystic fibrosis genotype with one Delta F508 allele and one unidentified allele and sweat sodium or chloride \> 60 mEq/L
4. Oxyhemoglobin saturation greater than or equal to 92% while breathing room air

Exclusion Criteria:

1. Underlying diseases likely to limit life span and/or increase risk of complications:

   1. Cancer requiring treatment in the past 5 years, with the exception of cancers that have been cured, or in the opinion of the investigator, carry a good prognosis such as non-melanoma skin cancer, papillary thyroid carcinoma, and cervical cancer in situ.
   2. GI disease

   i. Inflammatory bowel disease requiring treatment in the past year ii. elevations in ALT or AST levels to greater than 3 times the upper limit of normal
2. Conditions or behaviors likely to affect the conduct of the study

   1. Current or anticipated participation in another intervention research project
   2. Recent (with 2 months) sinus surgery or nasal polypectomy
   3. Currently pregnant or less than 3 months post-partum
   4. Currently nursing or within 6 weeks of having completed nursing
   5. Unwilling to undergo pregnancy testing or to report possible or confirmed pregnancy promptly during the course of the study
   6. Unwilling to use a reliable contraceptive method for two months after the completion of the study.
   7. Major psychiatric disorder, which, in the opinion of the investigators, would impede conduct of the study, e.g., alcoholism
   8. Other condition, which, in the opinion of the investigators, would impede conduct of the study.
3. Glucocorticoids other than topical, ophthalmic, and inhaled preparations.
4. Conditions that would place the patient at an increased risk for complications:

   1. Pneumothorax within the last 12 months
   2. Uncontrolled diabetes
   3. Asthma or allergic bronchopulmonary aspergillosis requiring systemic glucocorticoid therapy within the last two months
   4. Sputum culture growing a pathogen that does not have in vitro sensitivity to at least two types of antibiotics which could be administered to the patient
   5. History of major hemoptysis: (Greater than 240 mL of blood within a 24-hour period within the last 12 months).
5. Medication use or conditions not specifically mentioned above, including severe or end stage CF lung disease, that may serve as criteria for exclusion at the discretion of the investigators.
6. History of significant cardiovascular disease, such as myocardial infarction, congestive heart failure, unstable arrhythmia, or uncontrolled hypertension.
D: Inclusion Criteria:

* Confirmed diagnosis of CF
* Homozygous for the F508del CFTR mutation
* Forced expiratory volume in 1 second (FEV1) greater than or equal to (\>=) 40 percent (%) and less than or equal to (=\<) 90% of predicted normal for age, sex, and height
* Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Exclusion Criteria:

* An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
* History of solid organ or hematological transplantation
* History of alcohol or drug abuse in the past year
* Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
* Use of strong inhibitors, moderate inducers, or strong inducers of Cytochrome P450 3A (CYP3A) within 14 days before Day 1 of dosing

Answer: B