Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Study Evaluating the Efficacy and Safety of ALTU-135 Treatment in Patients With Cystic Fibrosis-Related Exocrine Pancreatic Insufficiency
Brief Summary: This is a clinical trial which will evaluate the efficacy of Liprotamase treatment in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (PI).


Options:
A: 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.
B: Inclusion Criteria:

* Signed informed consent given by the subject, or the parents, or a legally acceptable representative. If required by the Institutional Review Board/Ethics Committee (IRB/IEC), assent will be given by the subject
* Age ≥ 12 years
* Subjects who are able to swallow capsules with each meal and snacks
* Diagnosis of Cystic Fibrosis (CF) confirmed by two positive chloride sweat tests or gene analysis
* Diagnosis of pancreatic exocrine insufficiency proven by:

  1. Coefficient of fat absorption (CFA) \< 70% without supplementation
  2. or Human fecal elastase \< 50 μg/g stool
* Currently receiving treatment with a commercially available pancreatic enzyme product and on a continuous dose of this product for more than 3 months
* Clinically stable condition without evidence of acute respiratory disease within 1 month of enrollment
* Stable body weight defined as no more than a 5% decline within 3 months of enrolment
* Females of child-bearing potential should agree to continue using a medically acceptable method of birth control throughout the study and for 30 days immediately after the last dose of study drug. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (Depo-Provera™), an intrauterine device, or an oral contraceptive taken within the past 3 months where the subject agrees to continue using during the study or to adopt another birth control method, or a double-barrier method which consists of a combination of any two of the following: diaphragm, cervical cap, condom, or spermicide.

Exclusion Criteria:

* Evidence of cardiovascular, respiratory, urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except diabetes mellitus), neurologic/psychiatric, allergy, recent major surgery, or other relevant diseases as revealed by history, physical examination and/or laboratory assessments, which could limit participation in or completion of the study
* History of acute abdomen
* History of fibrosing colonopathy
* History of distal intestinal obstruction syndrome (DIOS) within 6 months prior to enrollment
* Solid organ transplant or surgery affecting the large bowel other than appendectomy
* Small bowel surgery that significantly affected absorptive capacity (e.g. gastrectomy or pancreatectomy)
* Pregnancy or lactation
* Any type of malignancy involving the digestive tract in the last 5 years
* Celiac disease or Crohn's disease
* Known allergy to pancreatin or inactive ingredients (excipients) of pancreatin capsules
* Suspected non-compliance or non-cooperation
* Intake of experimental drugs within 30 days prior to study start
* Mental disability or any other lack of fitness, in the Investigator's opinion, to preclude subject's participation in or ability to complete the study
* Diagnosis of human immunodeficiency virus in medical history.
C: Inclusion Criteria:

CF cohort:

Diagnosis of CF determined by

* a sweat chloride of \>60 mEq/L and/or
* detection of 2 disease causing CFTR mutations with evidence of organ involvement.

Healthy controls:

* Age-matched

Exclusion Criteria:

CF cohort:

* Lacking ability to cooperate of patients /their families, respectively

Healthy controls:

* Other diseases causing abdominal symptoms (Inflammatory bowel disease (IBD), alpha 1 antitrypsin deficiency, celiac disease, food allergy, gastroenteritis, etc.)
D: Inclusion Criteria:

* Females of childbearing potential must be willing to use birth control
* Diagnosis of CF based upon the following criteria:

  * two clinical features consistent with CF; and

    * either genotype with two identifiable mutations consistent with CF, OR
    * sweat chloride \>60 mEq/L by quantitative pilocarpine iontophoresis
* Clinically stable with no evidence of acute upper or lower respiratory tract infection
* PI determined by fecal elastase \<100 µg/g stool measured at screening
* Able to take pancreatic enzyme supplementation in the form of capsules
* Able to perform the testing (e.g., stool collections) and inpatient stays required for this study, as judged by the Investigator
* Baseline coefficient of fat absorption (CFA) less than or equal to 80%

Exclusion Criteria:

* CFA \>80% at Baseline
* Pregnancy, breastfeeding or of childbearing potential and not willing to use birth control during the study
* History of fibrosing colonopathy
* History of liver transplant, lung transplant or significant surgical resection of the bowel
* Any acute or chronic diarrheal illness unrelated to PI
* Unable to discontinue enteral tube feedings during the study
* Known hypersensitivity to food additives
* Inability to consume the diet required by the study, in the judgment of the Investigator
* Participation in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to screening
* Abnormal liver function (except for patients with Gilbert Syndrome)
* Signs and/or symptoms of liver cirrhosis, portal hypertension or documented liver disease unrelated to CF
* Distal intestinal obstruction syndrome (DIOS) in the last six months prior to screening
* Unable to discontinue the use of pancreatic enzymes
* Any condition that the Investigator believes would interfere with the intent of this study or would make participation not in the best interest of the patient
* Patient is unlikely to complete the study, as determined by the Investigator

Answer: D