Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Open-label, Drug-Drug Interaction Study to Assess the Steady State Pharmacokinetics of N91115 Alone and in the Presence of Multiple Dose Administration of Rifampin in Healthy Adult Subjects (SNO-5)
Brief Summary: The present study is designed to assess the effects of Rifampin on the pharmacokinetics of N91115 in healthy subjects.


Options:
A: Inclusion Criteria:

* Subject voluntarily agrees to participate in this study; signs an IRB-approved informed consent
* Subject is healthy as determined by the screening medical evaluation (including but not limited to medical history, physical examination and clinical laboratory evaluations)
* Subject is Caucasian
* Female subject must be of non-childbearing potential or post-menopausal
* Male subject must agree to use a condom with spermicide and refrain from sperm donation from Day -1 until 30 days post last dose or have a vasectomy at least 6 months prior to screening
* Subject is a non-smoker
* Subject has a body weight \> 45 kg and BMI between 18 and 32 kg/m2
* Subject has no clinically significant vital signs finding at screening or Day -1, per the investigator's judgment
* Subject has no clinically significant abnormal findings in 12-lead ECG , per the investigator's judgment, at screening

Exclusion Criteria:

* Subject has clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s)
* Subject has abnormal 12-lead ECG at screening per protocol
* Subject has any disorder that would interfere with the absorption, distribution, metabolism or excretion of drugs
* Subject has any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the clinical study
* Subject is a current alcohol abuser and/or has a history of illicit drug abuse within 1 year prior to dosing
* Subject has a positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody
* Subject is unwilling to refrain from consumption of coffee and caffeine-containing foods and beverages from Day -1 until discharge on Day 14
* Subject is unwilling to abstain from using alcohol beverages from Day -1 until discharge on Day 14
* Subject has donated blood (\> 500 mL) or blood products within 56 days prior to Day -1
* Subject has used over-the-counter (OTC) medications (including vitamins) from Day -7, or prescription medications, or herbal remedies from Day -14 until end-of-study follow-up call. By exception, acetaminophen ≤ 1000 mg/day is permitted except within 48 hours prior to Day -1 and hormone replacement therapy (HRT) is allowed throughout the study
* Subject has used an investigational drug within 30 days prior to Day 1 dosing
* Subject has a history of bleeding disorders
B: 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)
C: Inclusion Criteria:

* Aged 12 years and older
* Male or female Non-pregnant women who are to remain non-pregnant for 3 months after the end of the study. Women of childbearing potential must use a reliable method of contraception. Reliable methods of contraception for female patients include the following:
* barrier type devices (e.g., female condom, diaphragm and contraceptive sponge) used ONLY in combination with a spermicide
* intrauterine devices
* oral contraceptive agent
* Depo-Provera™ (medroxyprogesterone acetate)
* levonorgestrel implants Abstention, the rhythm method or contraception by the partner alone are NOT reliable methods of contraception. A woman is considered to have child-bearing potential unless she meets at least one of the following criteria:
* 6 weeks post-surgical bilateral salpingo-oophorectomy or hysterectomy
* Premature ovarian failure confirmed by a specialist gynecologist
* Age \> 50 years and not treated with any kind of HRT for at least 2 years prior to screening, and with amenorrhea for at least 24 consecutive months prior to screening and a serum FSH level of \> 40 IU/L at screening.
* Age \> 55 years and treated with HRT prior to screening with an appropriate medical documentation of spontaneous amenorrhea for at least 24 months. For female patients in the pediatric age range, a reliable method of contraception must be considered, if appropriate.

  * Male patients accepting for the duration of the study and for 3 months thereafter to use a condom and not to procreate a child (not in case of azoospermia)
  * Cystic fibrosis patients homozygous for the F508del mutation as confirmed by genetic test
  * Signed informed consent prior to any study-mandated procedure

Exclusion Criteria:

* Any condition prohibiting the correct measurement of the NPD such as upper respiratory tract infection
* Acute upper respiratory tract or pulmonary exacerbation requiring antibiotic intervention within 2 weeks of screening
* Severe renal impairment (creatinine clearance \< 30 mL/min as per Cockroft and Gault)
* Female patients of childbearing potential who will not undergo a pregnancy test prior to enrollment into the study
* History of significant lactose intolerance
* History of neuropathy
* Presence of clinically significant diarrhea (\> 3 liquid stools per day for \> 7 days) without definable cause within 1 month prior to screening
* Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
* FEV1 \< 25% of predicted normal
* Oxygen saturation at rest \< 88%
* Active or passive smoking as measured using the Smokelyzer®
* Hypersensitivity to miglustat or any excipients
* Planned treatment or treatment with another investigationaldrug or therapy (e.g., gene therapy) within 1 month prior to randomization
* Breast-feeding, pregnant women or women who plan to become pregnant during the course of the study.
D: Inclusion Criteria:

* CF as diagnosed by:

  1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
  2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
  3. Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
* PA present in expectorated sputum or throat swab culture at Screening.
* Participants must have received three or more courses of TIS within the previous 12 months.
* Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
* Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
* Ability to perform reproducible pulmonary function tests.
* Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.

Exclusion Criteria:

* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
* History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
* Known local or systemic hypersensitivity to monobactam antibiotics.
* Inability to tolerate inhalation of a short acting Beta-2 agonist.
* Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
* Changes in physiotherapy technique or schedule within 7 days before Screening or between Screening and the next visit.
* History of lung transplantation.
* A chest X-ray indicating abnormal findings at Screening or within the previous 90 days.
* Abnormal renal or hepatic function or serum chemistry at Screening (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
* Positive pregnancy test at Screening.
* Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable birth control.
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator would have interfered with participant treatment, assessment, or compliance with the protocol.

Answer: A