Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Brief Summary: The purpose of this study is to evaluate the efficacy and safety of VX-661 in combination with ivacaftor (IVA, VX-770) and IVA monotherapy in participants with Cystic Fibrosis (CF) who are heterozygous for F508del-CFTR allele and a second allele with a CFTR mutation predicted to have residual function.


Options:
A: Inclusion Criteria:

* Signed informed consent form (ICF), and where appropriate, signed assent form.
* Participants entering the Part A Treatment Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104 and elect to enroll in Part A treatment cohort.
* Participants entering the Part B Treatment Cohort: Completed 56 days of study drug treatment in Cohort 4 of Study 102 and elect to enroll in Part B treatment cohort.
* Participants entering the Part A Observational Cohort: Completed 24 weeks of study drug treatment in Study 103 or Study 104, but do not elect to enroll in the Part A Treatment Cohort or do not qualify to enroll in Part A treatment cohort.
* Willing to remain on a stable CF medication regimen through the end of study (Part A and Part B Treatment Cohorts only).

Exclusion Criteria:

* Any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant (e.g., cirrhosis with portal hypertension).
* Pregnant and nursing females. Females of childbearing potential must have a negative pregnancy test at the Day 1 Visit.
* History of drug intolerance in the prior study that would pose an additional risk to the participant in the opinion of investigator or Vertex.
* History of poor compliance with study drug and/or procedures in the previous study as deemed by the investigator.
* Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor, or studies requiring blood collections with or without administration of study drug)
B: Inclusion Criteria:

* Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function
* 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 during screening
* Sweat chloride value ≥60 millimole per liter (mmol/L) during screening OR as documented in the participant's medical record
* Stable CF disease as judged by the investigator

Exclusion Criteria:

* History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant
* An acute upper or lower respiratory infection, pulmonary exacerbation
* History of solid organ or hematological transplantation
* Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor \[VX-809\], and/or ivacaftor) within 30 days of screening
* Pregnant and nursing females
* Sexually active participants of reproductive potential who are not willing to follow the contraception requirements
C: Key Inclusion Criteria:

* Completed study drug treatment in parent study (VX18-445-109); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study

Key Exclusion Criteria:

* History of study drug intolerance in parent study

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

* Homozygous for F508del or heterozygous for F508del and an RF mutation (as defined in the protocol).
* Participants with ppFEV1 of ≥70 percentage points adjusted for age, sex, height.
* Participants with a screening LCI2.5 result ≥7.5.
* Participants who are able to swallow tablets.

Key Exclusion Criteria:

* Clinically significant cirrhosis with or without portal hypertension.
* Colonization with organisms associated with a more rapid decline in pulmonary status.
* Solid organ or hematological transplantation.

Other protocol defined Inclusion/Exclusion criteria may apply.

Answer: B