Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Multicenter, Two-period Crossover Study to Assess the Efficacy and Tolerability of NM-BL (Burlulipase) in Patients With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis
Brief Summary: The purpose of this Randomized, Double-blind, Multicenter, Two-period Crossover Study is to Assess the Efficacy and Tolerability of Burlulipase (NM-BL) in Patients with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis


Options:
A: Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
2. Age greater than or equal to 18y on date of consent
3. Pancreatic insufficiency
4. Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
5. For female subjects, negative urine pregnancy test at enrollment.

Control Subjects:

1. No history of cystic fibrosis.
2. Age ≥ 18y on date of consent.
3. Recent OGTT consistent with NGT.
4. For female subjects, negative urine pregnancy test at enrollment.

Exclusion Criteria:

1. Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
2. History of clinically symptomatic pancreatitis within last year
3. Prior lung or liver transplant
4. Severe CF liver disease, as defined by portal hypertension
5. Fundoplication-related dumping syndrome
6. Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
7. Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
8. Treatment with oral or intravenous corticosteroids within 6 weeks of study
9. Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
10. Abnormal renal function, within 90 days of Visit 1 or at Screening; defined as Creatinine greater than 2x upper limit of normal (ULN) or potassium greater than 5.5mEq/L on non-hemolyzed specimen
11. Inability to perform study specific procedures (MMTT, GPA)
12. Subjects, who in study team opinion, may be non-compliant with study procedures.

Control Subjects who will be exposed to GIP only:

1. History of clinically symptomatic pancreatitis.
2. History of liver disease.
3. 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 to the subject.
4. Hemoglobin \<10g/dL, within 90 days of GPA test or at Screening.
5. Abnormal renal function, within 90 days of GPA test or at Screening; defined as creatinine \> 2x upper limit of normal (ULN) or potassium \> 5.5mEq/L on non-hemolyzed specimen.
6. Inability to perform study specific procedures (MMTT, GPA).
7. subjects, who in study team opinion, may be non-compliant with study procedures.
8. elevation of serum amylase or lipase \> 1.5x ULN within 90 days of GPA test.
B: Inclusion Criteria:

1. Definitive diagnosis of CF based on the following:

   * One clinical feature consistent with CF and
   * Either a genotype with 2 identifiable mutations known to cause CF or a sweat chloride concentration \>60 mEq/L by pilocarpine iontophoresis
2. Pancreatic insufficiency documented by a monoclonal faecal elastase (FE) 100 μg/g stool at screening (test results within the previous 12 months are acceptable)
3. Currently receiving pancreatic enzyme replacement therapy
4. Adequate nutritional status based on the following: body mass index (BMI) \>19 kg/m2 in adult subjects or a BMI percentile 10th percentile for age in adolescent (12 to 17 years age group) subjects
5. Are clinically stable with no evidence of concomitant illness or acute upper or lower respiratory tract infection that requires antibiotics during the 7-day interval prior to screening and preceding entry into this clinical study

Exclusion Criteria:

1. Age \<12 years
2. Known contraindication, hypersensitivity, or intolerance to pork or other porcine PEPs
3. Current uncontrolled diabetes mellitus
4. History of solid organ transplantation
5. History of surgery affecting the bowel function and weight gain
C: Inclusion Criteria:

* Confirmed CF diagnosis by two positive chloride sweat tests or gene analysis
* Confirmed PEI by historical Coefficient of fat Absorption \< 70% without supplementation or current or historical fecal elastase \< 50µg/stool (within the last 12 months)
* Currently receiving treatment with a commercially available pancreatic enzyme product on a stable dose for more than 3 months
* Clinically stable condition without evidence of acute respiratory disease or any other acute condition
* Stable body weight and agrees to abstain from sexual activity

Exclusion Criteria:

* Ileus or acute abdomen
* History of fibrosing colonopathy, celiac disease, gastrectomy, Crohn´s disease and small bowel surgery other than minor resection due to meconium ileus without resulting in malabsorption syndrome
* History of distal ileal obstruction syndrome within 6 months of enrollment
* Use of an immunosuppressive drug
* Any type of malignancy involving the digestive tract in the last 5 years
* Known infection with HIV
D: Inclusion Criteria:

* Male and female patients aged ≥12 years from the date of informed consent
* Confirmed diagnosis of CF at screening
* Confirmed EPI by historical (within past 12 months) CFA \<70% without use of PERTs or current fecal elastase \<50 µg/g stool at screening
* Currently receiving PERT with a commercially available pancreatic enzyme
* Currently on stable treatment with proton pump inhibitors or H2 receptor antagonists
* Clinically stable condition without evidence of acute respiratory disease or any other acute condition

Exclusion Criteria:

* History of fibrosing colonopathy
* History of significant bowel resection, in the opinion of the investigator, or solid organ transplant
* History of being refractory to pancreatic enzyme replacement
* Current diagnosis or history of distal intestinal obstruction syndrome
* Current diagnosis of small intestinal bacterial overgrowth, ileus or acute abdomen
* A body mass index percentile \<10%

Answer: D