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:

* 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
B: Inclusion Criteria:

Subjects entering the Treatment Cohort must meet both of the following criteria:

* Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not permanently discontinue treatment
* Willing to remain on a stable CF medication through the Safety Follow-up Visit.

Subjects entering the Observational Cohort must meet 1 of the following criteria:

* Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow up in Study 011B.
* Received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B.

Exclusion Criteria (Treatment Cohort Only):

* History of 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 subject (e.g., cirrhosis with portal hypertension).
* Pregnant and nursing females.
* Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
* History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator
* History of poor compliance with study drug and/or procedure in the previous study as deemed by the investigator.
* Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor).
C: Key Inclusion Criteria:

* Part 1: Heterozygous for F508del and an MF mutation (F/MF)
* Part 2: Homozygous for F508del (F/F)
* FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height

Key Exclusion Criteria:

* History of clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* History of solid organ or hematological transplantation

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

* Documentation of a CF diagnosis as evidenced by 1 or more clinical features consistent with the CF phenotype and 1 or more of the following criteria:

  1. Sweat chloride equal to or greater than 60 mEq/L by quantitative pilocarpine iontophoresis test;
  2. Two well-characterized mutations in the CFTR gene
* FEV1 ≥ 40% predicted corrected
* Stable treatment of CF for 14 days before Visit 1

Exclusion Criteria:

* Severe or unstable CF, such as:

  1. Intravenous antibiotic treatment within 14 days before Visit 1
  2. Treatment with any corticosteroids \> 10 mg per day or \> 20 mg every other day oral prednisone or equivalent within 14 days before Visit 1
* Any one of the following values for laboratory tests at Screening:

  1. A positive pregnancy test (or at Visit 1);
  2. Hemoglobin \< 10 g/dL
  3. Neutrophils \< 1.0 x 10\~9/L
  4. Platelets \< 75 x 10\~9/L
  5. Creatinine clearance \< 50 ml/min according to modified Cockcroft-Gault equation
  6. Serum transaminases \> 2.5 x upper normal limit
  7. Total bilirubin ≥ 1.5 x upper limit of normal
* Any other condition that, in the opinion of the Principal Investigator, is clinically significant and may put the subject at greater safety risk, influence response to study product, or interfere with study assessments.

Answer: A