Open-Label Pilot Study With Crofelemer in Patients With Short Bowel Syndrome

Inclusion criteria

• Patients must understand and provide written informed consent before they can participate in the study. They must understand the study procedures of the trial and be willing to complete the required assessments;
• Male and female patients aged ≥ 18 years;
• SBS patients without colon in continuity:
• Patients with history of SBS resulting in intestinal failure caused by a major intestinal resection (e.g., injury, cancer, Crohn's disease, vascular disease, volvulus, intussusceptions or other causes). Diagnosis of SBS will be defined as remaining small bowel excluding colon in continuity and considered stable with regard to parenteral support (PS) need. Intestinal failure will be defined according to the recommendations of the American Society of Parenteral and Enteral Nutrition (ASPEN), i.e. a reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous (IV) supplementation is required to maintain health and/or growth;
• At least 6 months elapsed since last surgical bowel resection;
• No restorative surgery planned in the overall study period;
• Patients with at least 6 continuous months of PS dependency (parenteral nutrition and/or intravenous fluids) before entry in the study;
• Patients receiving stable PS (fluids, electrolytes or nutrients) at least three times per week to meet caloric, fluid or electrolytes needs with no major changes in provisions for at least 12 weeks;
• Patients with Crohn's disease will have to be in clinical remission for ≥ 12 weeks before entry in the study;
• Patients must be able to ingest solid or semi-solid foods and drink fluids;
• If female and of child-bearing potential, the patient use a highly effective method of birth control for the entire study duration. Highly effective birth control methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence;
• If female and of child-bearing potential, the patient must have a negative urine pregnancy test prior the first administration of the study drugs;
• Male patients must agree to use an acceptable form of birth control during the study and for 30 days after the last dose;
• Satisfactory general health status as determined by the investigator based on medical history and physical examination

Exclusion criteria

• Body mass index (BMI) \<17.5 or \>30 kg/m2;
• Presence of clinically significant intestinal adhesions and/or chronic abdominal pain that can interfere with the conduct of the study;
• Presence of confirmed active infection, temperatures \>100°Farenheit, or symptoms of an upper respiratory infection
• Patients with Radiological (Radiography and/or CT) signs of significant bowel dilatation or pseudo-obstruction;
• Active Crohn's disease as evaluated by standard procedures employed by the investigator;
• Inflammatory bowel disease (IBD) that required immunosuppressant therapy that has been introduced or changed within last 3 months or treatment with biologics within the last 6 months;
• Intestinal or other major surgery scheduled within the time frame of the study;
• Visible blood in the stool within the last 3 months;
• Ongoing radiation enteritis or the presence of damaged enteral tissue due to radiation enteritis, scleroderma, celiac disease, refractory or tropical sprue;
• Compromised immune system (e.g., acquired immune deficiency syndrome \[AIDS\], severe combined immunodeficiency);
• Inadequate hepatic function: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \>2 upper limit of normal (ULN), total bilirubin \>1.25 ULN or alkaline phosphatases \>2.5 ULN;
• Inadequate renal function: serum creatinine or blood urea nitrogen \>1.5 ULN;
• Urine sodium \<20 mmol/day;
• More than four SBS-related hospital admissions (unless one or more admissions were to rule out line sepsis) within the past 12 months or hospital admission within 1 month before screening;
• Previous use of Crofelemer or potential allergies to Crofelemer or its constituents;
• Use of infliximab, growth hormone or growth factors such as native glucagon-like peptide-2 (GLP-2) or other biological therapy within the last 12 weeks;
• Current or past use of teduglutide within the last 3 months;
• Use of systemic corticosteroids, methotrexate, cyclosporine, tacrolimus, sirolimus, octreotide, intravenous glutamine within the last 30 days;
• If taken at screening, use of antimotility and antidiarrheal agents (loperamide, difenoxylate, codeine and other opiates), H2-receptor antagonists, proton pump inhibitors, bile sequestering agents, oral glutamine, diuretics and oral rehydration solutions is required to be at stable average weekly doses for at least 4 weeks prior to screening evaluations and to remain stable for the entire study duration;
• Use of antibiotics within the last 30 days unless they were administered while ruling out line sepsis or for a dental procedure;
• Alcohol or drug abuse within the last year;
• Pregnant or lactating women;
• History of any malignancy in the past 1 year;
• History of psychiatric illnesses;
• History of any other uncontrolled chronic or acute concomitant disease which, in the Investigator's opinion, would contraindicate study participation or confound interpretation of the results;
• Patient not capable of understanding or not willing to adhere to the study visit schedules and other protocol requirements;
• Participation in any other interventional clinical study within 30 days prior to the screening visit.