Assessment of a PERT-free Nutritional Therapeutic Delivery System for Cystic Fibrosis

Randomized, Double-blind, Cross-over Trial Assessing a PERT-free Nutritional Therapeutic Delivery System for Cystic Fibrosis

This is a single center, randomized, double-blind, cross-over trial (with a follow-on single-blind safety evaluation stage), assessing a ready-to-drink nutritional supplement used without PERT ("PERT-free"), nutritional supplement for blood lipid levels, safety and tolerability compared to a standard of care nutritional supplement used concomitantly with PERT.

This is a single center, randomized, double-blind, cross-over trial (with a follow-on single-blind safety evaluation stage), assessing a ready-to-drink nutritional supplement used without PERT ("PERT-free"), nutritional supplement for blood lipid levels, safety and tolerability compared to a standard of care nutritional supplement used concomitantly with PERT.

The study hypothesis is that the PERT-free nutritional supplement will be equivalent to, or superior to, a standardized nutritional shake with regard to fat absorption, as indicated by blood lipid (triglyceride) levels while maintaining tolerability and safety without the use of PERT. The objective is to evaluate efficacy, safety, and tolerability of a "PERT-free" nutritional shake compared to a standard nutritional shake used concomitantly with PERT. Measurements include components of a standard lipid blood panel (triglycerides, cholesterol, HDL cholesterol, LDL cholesterol, and VLDL cholesterol), absorption of fat-soluble vitamins (vitamin D) and symptoms associated with EPI. Other objectives include evaluating palatability and patients' impressions of the products.

Inclusion Criteria:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, aged 12 years or older.
• Diagnosis of cystic fibrosis
• Currently receiving treatment with a commercially available pancreatic enzyme 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 5% decline within 3 months of enrollment.
• 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.
• Ability to take oral medication and oral liquid nutritional supplements and be willing to adhere to the study interventions.
• Agreement to adhere to Lifestyle Considerations as defined by the study protocol throughout the duration of the study.

Exclusion Criteria:

• Evidence of cardiovascular, respiratory (except underlying disease), urogenital, gastrointestinal/hepatic (except underlying disease), hematologic/immunologic, head, ears, eyes, nose, throat, dermatologic/connective tissue, musculoskeletal, metabolic/nutritional (except underlying disease), endocrine (except controlled diabetes mellitus), neurologic/psychiatric, milk, nut or soy allergies, 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 in the last year.
• 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).
• Intestinal inflammatory diseases including chronic diarrheal illness unrelated to pancreatic insufficiency.
• Celiac disease or Crohn's disease.
• Receiving enteral tube feeds for ≥50% of daily calorie intake.
• Pregnancy or lactation.
• Any type of malignancy involving the digestive tract in the last 5 years.
• 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.
• Listed for lung transplantation or other solid organ transplant or documented forced expiratory volume (FEV) ≤25%.
• Use of lipid lowering therapy including statins, fibrates, niacin, and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors that cannot be held at least 14 days prior to Day 1 and through Day 15 of the study.