Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2, Multicenter, Double-Blinded, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Lumacaftor Monotherapy, and Lumacaftor and Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Brief Summary: The purpose of this study is to evaluate of the safety, efficacy, pharmacokinetics (PK) and pharmacodynamic (PD) effects of lumacaftor (VX-809) alone and when coadministered with ivacaftor (VX-770) in participants with cystic fibrosis, homozygous or heterozygous for the F508del-CFTR mutation.


Options:
A: Inclusion Criteria:

* Ability to provide written informed consent (parental/guardian consent and participant assent if \<18 years of age)
* Age ≥6 years
* Body weight ≥16 kg
* Abnormal nasal transepithelial potential difference (TEPD) total chloride conductance (a less electrically negative value than -5 millivolts (mV) for total chloride conductance \[Δchloride-free+isoproterenol\])
* Sweat chloride \>40 milliequivalents/liter (mEq/L)
* Documentation of the simultaneous presence of a nonsense mutation in at least 1 allele of the CFTR gene and a CF-causing mutation in the other CFTR allele, as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization
* Verification that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the CFTR gene
* Ability to perform a valid, reproducible spirometry test using the study-specific spirometer with demonstration of an FEV1 ≥40% and ≤90% of predicted for age, gender, and height
* Resting oxygen saturation (as measured by pulse oximetry) ≥92% on room air
* Documentation by VivoMetrics that the participant has satisfactorily completed a 24-hour LifeShirt® cough frequency assessment
* Confirmed screening laboratory values within the central laboratory ranges (hepatic, adrenal, renal, serum electrolytes, and reproduction \[women only\] parameters)
* In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during the study drug administration and 4-week follow-up period
* Willingness and ability to comply with scheduled visits, drug administration plan, study restrictions, and study procedures

Exclusion Criteria:

* Known hypersensitivity to any of the ingredients or excipients of the study drug
* Any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiation) in a chronic treatment/prophylaxis regimen for CF or for CF-related conditions within 4 weeks prior to start of study treatment
* Exposure to another investigational drug within 4 weeks prior to start of study treatment
* Treatment with systemic aminoglycoside antibiotics at the time of the Baseline TEPD assessment
* Treatment with intravenous antibiotics within 3 weeks prior to start of study treatment
* History of solid organ or hematological transplantation
* Ongoing immunosuppressive therapy (other than corticosteroids)
* Ongoing warfarin, phenytoin, or tolbutamide therapy
* Ongoing participation in any other therapeutic clinical trial
* Major complications of lung disease (including massive hemoptysis, pneumothorax, or pleural effusion) within 8 weeks prior to start of study treatment
* Evidence of pulmonary exacerbation or acute upper or lower respiratory tract infection (including viral illnesses) within 3 weeks prior to randomization
* Known portal hypertension
* Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test
* Pregnancy or breast-feeding
* Current smoker or a smoking history of ≥10 pack-years (number of cigarette packs/day \* number of years smoked)
* Prior or ongoing medical condition (for example, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, electrocardiography 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.
B: Inclusion Criteria:

* Male or female participants with confirmed diagnosis of CF
* Must have the F508del-CFTR mutation on at least 1 allele.
* FEV1 greater than equal (\>=) 40% of predicted normal for age, gender, and height (Knudson standards)(Cohort 1, 2, and 3); FEV1 40-90% of predicted normal for age, gender, and height (Hankinson standards (Cohort 4)
* Participant of child-bearing potential and who are sexually active must meet the contraception requirements

Exclusion Criteria:

* History of any illness or condition 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).
* An acute illness including acute upper or lower respiratory infection, pulmonary exacerbation or changes in therapy (including antibiotics) for pulmonary disease within 14 days (Cohort 1, 2, and 3) or 28 days (Cohort 4) before receiving the first dose of study drug.
* History of solid organ or hematological transplantation.
* History of alcohol abuse or drug addiction in the past year, including cannabis, cocaine, and opiates.
* Ongoing participation in another therapeutic clinical study, or prior participation in an investigational drug study without appropriate washout
* Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of non-hormonal contraception
* Participants enrolled in Cohort 1 or Cohort 2 will not be eligible for Cohort 3
* Ongoing or prior participation in an investigational drug study within 30 days of the Screening Visit
* Heterozygous participants who participated in Cohort 2 and meet the eligibility criteria for Cohort 4 may participate in Cohort 4
* Evidence of lens opacity or cataract as determined by the ophthalmologic examination (Cohort 4 only)
C: Inclusion Criteria:

* Cystic fibrosis patients homozygous for the F508del mutation as confirmed by genetic test
* Aged 14 years and older
* Male or female (non-pregnant women who are to remain non-pregnant for 3 months after the end of the study)
* FEV1 \> 50% of predicted normal

Exclusion Criteria:

* Acute respiratory tract infection or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of visit 1
* Any condition prohibiting the correct measurement of the NPD such as respiratory tract infection
* Active or passive smoking
* Allergic chronic rhinitis
* History of significant lactose intolerance
* History of neuropathy
* History of cataracts or known increased risk of cataract formation
* Hypersensitivity to miglustat or any excipients
* Planned treatment or treatment with another investigational drug or therapy within 1 month prior to randomisation
D: Key Inclusion Criteria:

* Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes)
* Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height.

Key Exclusion Criteria:

* Clinically significant cirrhosis with or without portal hypertension
* Lung infection 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